Updated on 2025/07/02

写真a

 
MATSUMOTO Sohkichi
 
Organization
Academic Assembly Institute of Medicine and Dentistry IGAKU KEIRETU Professor
Graduate School of Medical and Dental Sciences Community Disease Control Infectious Disease Control and International Medicine Professor
Title
Professor
Homepage
http://www.med.niigata-u.ac.jp/eng/research/kiso/saikin.html
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External link

Degree

  • Doctor (Medicine) ( 1998.12   Nagasaki University )

  • Doctor (Dentistry) ( 1999.9   Nagasaki University )

Research Interests

  • Development of diagnosis of mycobacterial diseases

  • Host immunity and Vaccine Development against tuberculosis

  • Drug development against mycobacterial diseases

  • mycobacteria

  • Bacteria

  • dormancy and latent infection

  • tuberculosis

  • persister

  • Infectious diseases

  • Mycobacterium

Research Areas

  • Life Science / Bacteriology

  • Life Science / Immunology

Research History (researchmap)

  • Hokkaido University

    2023.4

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  • Airlangga University   Adjunct Professor

    2018.10

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    Country：Indonesia

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  • 大阪公立(市立)大学   大学院医学研究科   客員教授

    2014.4

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  • Niigata University   School of Medicine, Faculty of Medicine   Professor

    2013.9

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  • Osaka City University   med, Medical School   Associate Professor

    2007.4 - 2013.8

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  • Osaka City University   med, Medical School   Associate Professor (as old post name)

    2006.1 - 2006.12

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  • Osaka City University   med, Medical School   Lecturer

    2002.1 - 2005.12

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  • National Institutes of Health

    1999.10 - 2001.12

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  • Nakagaki University   Research Assistant

    1992.9 - 1999.9

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Research History

  • Niigata University   Graduate School of Medical and Dental Sciences Community Disease Control Infectious Disease Control and International Medicine   Professor

    2013.9

Education

  • Nagasaki University   Faculty of Dentistry

    1986.4 - 1992.3

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    Country： Japan

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Professional Memberships

  • THE JAPANESE SOCIETY FOR IMMUNOLOGY

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  • THE MOLECULAR BIOLOGY SOCIETY OF JAPAN

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  • THE JAPANESE SOCIETY FOR BIOFILM RESEARCH

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  • JAPANESE SOCIETY FOR BACTERIOLOGY

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Committee Memberships

  • Japanese Society for Bacteriology   director  

    2024.1   

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    Committee type：Academic society

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  • 「感染症研究教育拠点連合」感染症戦略協議会   アドバイザリーボード  

    2024.1   

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  • Mycobacterial Diseases panel, US-Japan Cooperative Medical Science Program   Chair  

    2023.4   

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    Committee type：Other

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  •   Member  

    2016.7   

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    Committee type：Other

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  • 日本バイオフィルム学会   理事  

    2014.4   

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    Committee type：Academic society

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  • U.S.-Japan Cooperative Medical Sciences Program, Tuberculosis & Leprosy   Panel  

    2012.4 - 2023.3   

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  • 日本細菌学会   評議員  

    2009   

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    Committee type：Academic society

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Studying abroad experiences

  • National Institues of Health   Research fellow

    1999.10 - 2001.12

 

Papers

  • Potential Role of Whole Genome Sequencing to Predict the Virulence, Anti-TB Resistance, and Variants of Mycobacterium tuberculosis Strains from Rifampicin-sensitive Pulmonary Tuberculosis Patients in Surabaya, East Java, Indonesia Reviewed

    Ni Made Mertaniasih, Muhamad Frendy Setyawan, Ummi Amaliatush Sholichah Putri Merdekawati, Nurul Wiqoyah, Deby Kusumaningrum, Irfan Arif Ikhwani, Sohkichi Matsumoto

    The International Journal of Mycobacteriology   14 ( 2 )   153 - 163   2025.4

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    Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

    Background:

    Tuberculosis (TB) is the second concern of a fatal infectious disease in the world caused by Mycobacterium tuberculosis (MTB). Indonesia has many regions that is known as a hotspot region for MTB cases, one of the most cities high newly case detected in 5 years was Surabaya. In 2022, Surabaya reported a higher pulmonary TB (PTB) prevalence rate of 0.35%. This study aimed to investigate the genomic and phylogenetic characteristics of MTB from isolates of rifampicin-sensitive PTB patients in Surabaya using whole genome sequencing (WGS).

    Methods:

    This study is a cross-sectional study to descriptively analyses WGS data using bioinformatics. Out of 8 enrolled drug-sensitive PTB patients; however, only three cultured isolates successfully grew on MB 7H11/OADC agar and subjected for WGS analysis.

    Results:

    Whole genome analysis revealed that all the samples were drug sensitive. The identified samples were majority belonged to lineage 4.4.1 (Euro-American [S-type]) and we found a novel strain in East Java region known as Lineage 4.10 (Euro-American [Uganda 1]). In addition, we identified a novel SNVs predicted to be associated with genomic adaptation in fgd1, embC, embA, and rv0565c under antibiotic pressures.

    Conclusion:

    WGS predicts that all the samples from pulmonary rifampicin-sensitive TB patients in this study were drug sensitive. We report the first discovery of a novel L4.10 strain, classified as Uganda 1, in Surabaya, Indonesia.

    DOI： 10.4103/ijmy.ijmy_54_25

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  • BCG-derived acellular membrane vesicles elicit antimycobacterial immunity and innate immune memory. International journal

    Takehiro Yamaguchi, Noriaki Samukawa, Sohkichi Matsumoto, Masayuki Shiota, Masaki Matsumoto, Ryoma Nakao, Satoru Hirayama, Yutaka Yoshida, Akihito Nishiyama, Yuriko Ozeki, Shuhei Tomita

    Frontiers in immunology   16   1534615 - 1534615   2025

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

    Tuberculosis (TB) is one of the leading causes of death due to infectious disease. The sole established vaccine against TB is the Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine. However, owing to the lack of durable immunity with the BCG vaccine and its risk of infection, safer vaccines that can also be used as boosters are needed. Here, we examined whether membrane vesicles (MVs) from BCG (BCG-MVs) isolated from BCG statically cultured in nutrient-restricted Sauton's medium (s-MVs) and from BCG planktonically cultured in nutrient-rich medium commonly used in the laboratory (p-MVs) could be used as novel TB vaccines. MVs are extracellular vesicles produced by various bacteria, including mycobacteria. Differences in the culture conditions affected the morphology, contents, immunostimulatory activity and immunogenicity of BCG-MVs. s-MVs presented greater immunostimulatory activity than p-MVs via the induction of TLR2 signaling. Mouse immunization experiments revealed that s-MVs, but not p-MVs, induced mycobacterial humoral and mucosal immunity, especially when administered in combination with adjuvants. In a BCG challenge experiment using BCG Tokyo type I carrying pMV361-Km, subcutaneous vaccination with s-MVs reduced the bacterial burden in the mouse lung to a level similar to that after intradermal vaccination with live BCG. Furthermore, the administration of s-MVs induced a significant lipopolysaccharide-induced proinflammatory response in macrophages in vitro. These results indicate that BCG-MVs obtained from static culture in Sauton's medium induce not only humoral immunity against mycobacteria but also trained immunity, which can allow the clearance of infectious agents other than mycobacteria. Together, these findings highlight the immunological properties of BCG-MVs and the availability of acellular TB vaccines that confer broad protection against various infectious diseases.

    DOI： 10.3389/fimmu.2025.1534615

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  • Functional genomics reveals the mechanism of hypoxic adaptation in nontuberculous mycobacteria Reviewed

    Yoshitaka Tateishi, Yuriko Ozeki, Akihito Nishiyama, Yuta Morishige, Yusuke Minato, Anthony D Baughn, Sohkichi Matsumoto

    2024.7

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    Authorship：Last author   Publishing type：Research paper (scientific journal)   Publisher：eLife Sciences Publications, Ltd  

    DOI： 10.7554/elife.99426.1.sa3

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  • Recombinant mycobacterial DNA-binding protein 1 with post-translational modifications boosts IFN-gamma production from BCG-vaccinated individuals' blood cells in combination with CpG-DNA. International journal

    Yuriko Ozeki, Akira Yokoyama, Akihito Nishiyama, Yutaka Yoshida, Yukiko Ohara, Tsukasa Mashima, Chikako Tomiyama, Amina K Shaban, Atsuki Takeishi, Mayuko Osada-Oka, Takehiro Yamaguchi, Yoshitaka Tateishi, Jun-Ichi Maeyama, Mariko Hakamata, Hiroshi Moro, Toshiaki Kikuchi, Daisuke Hayashi, Fumiko Suzuki, Toshiko Yamamoto, Sumiko Iho, Masato Katahira, Saburo Yamamoto, Sohkichi Matsumoto

    Scientific reports   14 ( 1 )   9141 - 9141   2024.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    Tuberculosis remains a large health threat, despite the availability of the tuberculosis vaccine, BCG. As BCG efficacy gradually decreases from adolescence, BCG-Prime and antigen-booster may be an efficient strategy to confer vaccine efficacy. Mycobacterial DNA-binding protein 1 (MDP1, namely Rv2986c, hupB or HU) is a major Mycobacterium tuberculosis protein that induces vaccine-efficacy by co-administration with CpG DNA. To produce MDP1 for booster-vaccine use, we have created recombinant MDP1 produced in both Escherichia coli (eMDP1) and Mycolicibacterium smegmatis (mMDP1), an avirulent rapid-growing mycobacteria. We tested their immunogenicity by checking interferon (IFN)-gamma production by stimulated peripheral blood cells derived from BCG-vaccinated individuals. Similar to native M. tuberculosis MDP1, we observed that most lysin resides in the C-terminal half of mMDP1 are highly methylated. In contrast, eMDP1 had less post-translational modifications and IFN-gamma stimulation. mMDP1 stimulated the highest amount of IFN-gamma production among the examined native M. tuberculosis proteins including immunodominant MPT32 and Antigen 85 complex. MDP1-mediated IFN-gamma production was more strongly enhanced when combined with a new type of CpG DNA G9.1 than any other tested CpG DNAs. Taken together, these results suggest that the combination of mMDP1 and G9.1 possess high potential use for human booster vaccine against tuberculosis.

    DOI： 10.1038/s41598-024-58836-8

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  • Evaluation of cytokine profiles related to Mycobacterium tuberculosis latent antigens using a whole-blood assay in the Philippines

    Ikkoh Yasuda, Naomi Ruth D. Saludar, Ana Ria Sayo, Shuichi Suzuki, Akira Yokoyama, Yuriko Ozeki, Haruka Kobayashi, Akihito Nishiyama, Sohkichi Matsumoto, Sharon E. Cox, Takeshi Tanaka, Yoshiro Yamashita

    Frontiers in Immunology   15   2024.4

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    Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

    Introduction

    There is no useful method to discriminate between latent tuberculosis infection (LTBI) and active pulmonary tuberculosis (PTB). This study aimed to investigate the potential of cytokine profiles to discriminate between LTBI and active PTB using whole-blood stimulation with Mycobacterium tuberculosis (MTB) antigens, including latency-associated antigens.

    Materials and methods

    Patients with active PTB, household contacts of active PTB patients and community exposure subjects were recruited in Manila, the Philippines. Peripheral blood was collected from the participants and used for whole-blood stimulation (WBS) with either the early secretory antigenic target and the 10-kDa culture filtrate protein (ESAT-6/CFP-10), Rv3879c or latency-associated MTB antigens, including mycobacterial DNA-binding protein 1 (MDP-1), α-crystallin (Acr) and heparin-binding hemagglutinin (HBHA). Multiple cytokine concentrations were analyzed using the Bio-Plex™ multiplex cytokine assay.

    Results

    A total of 78 participants consisting of 15 active PTB patients, 48 household contacts and 15 community exposure subjects were eligible. The MDP-1-specific IFN-γ level in the active PTB group was significantly lower than that in the household contact group (p < 0.001) and the community exposure group (p < 0.001). The Acr-specific TNF-α and IL-10 levels in the active PTB group were significantly higher than those in the household contact (TNF-α; p = 0.001, IL-10; p = 0.001) and community exposure (TNF-α; p < 0.001, IL-10; p = 0.01) groups. However, there was no significant difference in the ESAT-6/CFP-10-specific IFN-γ levels among the groups.

    Conclusion

    The patterns of cytokine profiles induced by latency-associated MTB antigens using WBS have the potential to discriminate between LTBI and active PTB. In particular, combinations of IFN-γ and MDP-1, TNF-α and Acr, and IL-10 and Acr are promising. This study provides the first demonstration of the utility of MDP-1-specific cytokine responses in WBS.

    DOI： 10.3389/fimmu.2024.1330796

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  • Genetic engineering employing MPB70 and its promoter enables efficient secretion and expression of foreign antigen in bacillus Calmette Guérin (BCG) Tokyo

    Atsuki Takeishi, Amina K. Shaban, Taichi Kakihana, Hayato Takihara, Shujiro Okuda, Hidekazu Osada, Desak Nyoman Surya Suameitria Dewi, Yuriko Ozeki, Yutaka Yoshida, Akihito Nishiyama, Yoshitaka Tateishi, Yuki Aizu, Yasushi Chuma, Kazuyo Onishi, Daisuke Hayashi, Saburo Yamamoto, Tetsu Mukai, Manabu Ato, Duong Huu Thai, Huynh Thi Thao Nhi, Tsuyoshi Shirai, Satoshi Shibata, Fumiko Obata, Jun Fujii, Seiya Yamayoshi, Maki Kiso, Sohkichi Matsumoto

    Microbiology and Immunology   2024.1

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    Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    Abstract

    Vaccination is an important factor in public health. The recombinant bacillus Calmette Guérin (rBCG) vaccine, which expresses foreign antigens, is expected to be a superior vaccine against infectious diseases. Here, we report a new recombination platform in which the BCG Tokyo strain is transformed with nucleotide sequences encoding foreign protein fused with the MPB70 immunogenic protein precursor. By RNA‐sequencing, mpb70 was found to be the most transcribed among all known genes of BCG Tokyo. Small oligopeptide, namely, polyhistidine tag, was able to be expressed in and secreted from rBCG through a process in which polyhistidine tag fused with intact MPB70 were transcribed by an mpb70 promoter. This methodology was applied to develop an rBCG expressing the receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2. Immunoblotting images and mass spectrometry data showed that RBD was also secreted from rBCG. Sera from mice vaccinated with the rBCG showed a tendency of weak neutralizing capacity. The secretion was retained even after a freeze‐drying process. The freeze‐dried rBCG was administered to and recovered from mice. Recovered rBCG kept secreting RBD. Collectively, our recombination platform offers stable secretion of foreign antigens and can be applied to the development of practical rBCGs.

    DOI： 10.1111/1348-0421.13116

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  • Association between diet quality and risk of stunting among school-aged children in Schistosoma mansoni endemic area of western Kenya: a cross-sectional study.

    Madoka Kishino, Azumi Hida, Evans A Chadeka, Manabu Inoue, Mayuko Osada-Oka, Sohkichi Matsumoto, Sammy M Njenga, Shinjiro Hamano, Sachiyo Nagi

    Tropical medicine and health   52 ( 1 )   12 - 12   2024.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    BACKGROUND: Healthy eating habits are essential for improving nutritional status and strengthening immunity against infectious diseases. This study examined the relationship between diet quality and stunting in school-aged children in an infectious disease-endemic area of western Kenya. METHODS: This cross-sectional study included 260 school-aged children (age 9-17 years) enrolled in primary schools in Mbita Sub-county, western Kenya. The nutritional status was assessed using anthropometric measurements. Dietary intake was measured using food frequency questionnaires and evaluated using the Food Pyramid (FP) score, which indicates adherence to the Kenyan food-based dietary guideline. Information on the children's age, sex, maternal education, and household wealth index was collected using a household-based questionnaire. Infections with the predominant parasites, such as Schistosoma (S.) mansoni, were detected via microscopy. The trend associations of the FP score with food group intake were examined to characterize the dietary intake of this population. Logistic regression analysis was performed to investigate the relationship between stunting and FP score tertiles, adjusted for sociodemographic and economic indicators and parasitic infection status. RESULTS: Among the studied schoolchildren, 15.0% exhibited stunting, while 76.2% were infected with S. mansoni. The mean FP score was 25.6 out of 50 points. A higher FP score was characterized by a high intake of roots and tubers, dairy products, pulses, and fruits and a low intake of cereals and animal-source foods. The analysis revealed a trend: a lower risk of stunting was evident in groups with elevated FP scores (p for trend = 0.065). However, these trend associations were observable among subjects with either negative or light S. mansoni infection (p for trend = 0.016). CONCLUSIONS: A higher quality diet, as evaluated by FP scores, was associated with a low risk of stunting among school-aged children. Notably, this association seemed to weaken in the presence of a high burden of S. mansoni infection. It highlights the importance of enhancing dietary quality through the promotion of diverse nutrient-dense foods alongside effective S. mansoni infection control for improved growth. This study contributes fundamental knowledge for understanding the diet-malnutrition relationship in areas endemic for S. mansoni infection.

    DOI： 10.1186/s41182-023-00566-0

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  • Dynamic action of an intrinsically disordered protein in DNA compaction that induces mycobacterial dormancy. International journal

    Akihito Nishiyama, Masahiro Shimizu, Tomoyuki Narita, Noriyuki Kodera, Yuriko Ozeki, Akira Yokoyama, Kouta Mayanagi, Takehiro Yamaguchi, Mariko Hakamata, Amina Kaboso Shaban, Yoshitaka Tateishi, Kosuke Ito, Sohkichi Matsumoto

    Nucleic acids research   2023.12

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    Mycobacteria are the major human pathogens with the capacity to become dormant persisters. Mycobacterial DNA-binding protein 1 (MDP1), an abundant histone-like protein in dormant mycobacteria, induces dormancy phenotypes, e.g. chromosome compaction and growth suppression. For these functions, the polycationic intrinsically disordered region (IDR) is essential. However, the disordered property of IDR stands in the way of clarifying the molecular mechanism. Here we clarified the molecular and structural mechanism of DNA compaction by MDP1. Using high-speed atomic force microscopy, we observed that monomeric MDP1 bundles two adjacent DNA duplexes side-by-side via IDR. Combined with coarse-grained molecular dynamics simulation, we revealed the novel dynamic DNA cross-linking model of MDP1 in which a stretched IDR cross-links two DNA duplexes like double-sided tape. IDR is able to hijack HU function, resulting in the induction of strong mycobacterial growth arrest. This IDR-mediated reversible DNA cross-linking is a reasonable model for MDP1 suppression of the genomic function in the resuscitable non-replicating dormant mycobacteria.

    DOI： 10.1093/nar/gkad1149

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  • Limited proteolysis of mycobacterial DNA-binding protein 1 with an extended, lysine-rich, intrinsically disordered region to unveil posttranslational modifications

    Yutaka Yoshida, Akihito Nishiyama, Desak Nyoman Surya Suameitria Dewi, Tomoya Yamazaki, Akira Yokoyama, Daiki Kobayashi, Hitoshi Kondo, Yuriko Ozeki, Sohkichi Matsumoto

    Biochemical and Biophysical Research Communications   2023.9

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    Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.bbrc.2023.09.028

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  • Mycobacterial DNA-binding protein 1 is critical for BCG survival in stressful environments and simultaneously regulates gene expression. International journal

    Amina K Shaban, Gebremichal Gebretsadik, Mariko Hakamata, Hayato Takihara, Erina Inouchi, Akihito Nishiyama, Yuriko Ozeki, Yoshitaka Tateishi, Yukiko Nishiuchi, Takehiro Yamaguchi, Naoya Ohara, Shujiro Okuda, Sohkichi Matsumoto

    Scientific reports   13 ( 1 )   14157 - 14157   2023.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    Survival of the live attenuated Bacillus Calmette-Guérin (BCG) vaccine amidst harsh host environments is key for BCG effectiveness as it allows continuous immune response induction and protection against tuberculosis. Mycobacterial DNA binding protein 1 (MDP1), a nucleoid associated protein, is essential in BCG. However, there is limited knowledge on the extent of MDP1 gene regulation and how this influences BCG survival. Here, we demonstrate that MDP1 conditional knockdown (cKD) BCG grows slower than vector control in vitro, and dies faster upon exposure to antibiotics (bedaquiline) and oxidative stress (H2O2 and menadione). MDP1-cKD BCG also exhibited low infectivity and survival in THP-1 macrophages and mice indicating possible susceptibility to host mediated stress. Consequently, low in vivo survival resulted in reduced cytokine (IFN-gamma and TNF-alpha) production by splenocytes. Temporal transcriptome profiling showed more upregulated (81-240) than downregulated (5-175) genes in response to MDP1 suppression. Pathway analysis showed suppression of biosynthetic pathways that coincide with low in vitro growth. Notable was the deferential expression of genes involved in stress response (sigI), maintenance of DNA integrity (mutT1), REDOX balance (WhiB3), and host interactions (PE/PE_PGRS). Thus, this study shows MDP1's importance in BCG survival and highlights MDP1-dependent gene regulation suggesting its role in growth and stress adaptation.

    DOI： 10.1038/s41598-023-40941-9

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  • Antibodies against native proteins of Mycobacterium tuberculosis can detect pulmonary tuberculosis patients

    Desak Nyoman Surya Suameitria Dewi, Ni Made Mertaniasih, Soedarsono, Kimika Hagino, Tomoya Yamazaki, Yuriko Ozeki, Wayan Tunas Artama, Haruka Kobayashi, Erina Inouchi, Yutaka Yoshida, Satoshi Ishikawa, Amina Kaboso Shaban, Yoshitaka Tateishi, Akihito Nishiyama, Manabu Ato, Sohkichi Matsumoto

    Scientific Reports   2023.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    <jats:title>Abstract</jats:title><jats:p>Accurate point-of-care testing (POCT) is critical for managing tuberculosis (TB). However, current antibody-based diagnosis shows low specificity and sensitivity. To find proper antigen candidates for TB diagnosis by antibodies, we assessed IgGs responsiveness to <jats:italic>Mycobacterium tuberculosis</jats:italic> proteins in pulmonary TB (PTB) patients. We employed major secreted proteins, such as Rv1860, Ag85C, PstS1, Rv2878c, Ag85B, and Rv1926c that were directly purified from <jats:italic>M. tuberculosis</jats:italic>. In the first screening, we found that IgG levels were significantly elevated in PTB patients only against Rv1860, PstS1, and Ag85B among tested antigens. However, recombinant PstS1 and Ag85B from <jats:italic>Escherichia coli (E. coli)</jats:italic> couldn’t distinguish PTB patients and healthy controls (HC). Recombinant Rv1860 was not checked due to its little expression. Then, the 59 confirmed PTB patients from Soetomo General Academic Hospital, Surabaya, Indonesia, and 102 HC were tested to Rv1860 and Ag85B only due to the low yield of the PstS1 from <jats:italic>M. tuberculosis</jats:italic>. The ROC analysis using native Ag85B and Rv1860 showed an acceptable area under curve for diagnosis, which is 0.812 (95% CI 0.734–0.890, <jats:italic>p</jats:italic> &lt; 0.0001) and 0.821 (95% CI 0.752–0.890, <jats:italic>p</jats:italic> &lt; 0.0001). This study indicates that taking consideration of native protein structure is key in developing TB’s POCT by antibody-based diagnosis.</jats:p>

    DOI： 10.1038/s41598-023-39436-4

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  • Virulence of Mycobacterium intracellulare clinical strains in a mouse model of lung infection - role of neutrophilic inflammation in disease severity. International journal

    Yoshitaka Tateishi, Yuriko Ozeki, Akihito Nishiyama, Mari Miki, Ryoji Maekura, Hiroshi Kida, Sohkichi Matsumoto

    BMC microbiology   23 ( 1 )   94 - 94   2023.4

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    BACKGROUND: Mycobacterium intracellulare is a major etiological agent of Mycobacterium avium-intracellulare pulmonary disease (MAC-PD). However, the characteristics of the virulence of M. intracellulare and the in vivo chemotherapeutic efficacy remain unclear. In this study, we examined the virulence of nine M. intracellulare strains with different clinical phenotypes and genotypes in C57BL/6 mice. RESULTS: We classified three types of virulence phenotypes (high, intermediate, and low) based on the kinetics of the bacterial load, histological lung inflammation, and neutrophilic infiltration. High virulence strains showed more severe neutrophilic infiltration in the lungs than intermediate and low virulence strains, with 6.27-fold and 11.0-fold differences of the average percentage of neutrophils in bronchoalveolar lavage fluid, respectively. In particular, the high virulence strain M.i.198 showed the highest mortality in mice, which corresponded to the rapid progression of clinical disease. In mice infected with the drug-sensitive high virulence strain M019, clarithromycin-containing chemotherapy showed the highest efficacy. Monotherapy with rifampicin exacerbated lung inflammation with increased lymphocytic and neutrophilic infiltration into the lungs. CONCLUSIONS: The virulence phenotypes of clinical strains of M. intracellulare were diverse, with high virulence strains being associated with neutrophilic infiltration and disease progression in infected mice. These high virulence strains were proposed as a useful subject for in vivo chemotherapeutic experiments.

    DOI： 10.1186/s12866-023-02831-y

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  • Antigen-specific cytokine profiles for pulmonary Mycobacterium avium complex disease stage diagnosis. International journal

    Yoshiro Yamashita, Ikkoh Yasuda, Takeshi Tanaka, Toru Ikeda, Mayumi Terada, Masahiro Takaki, Yoshiko Tsuchihashi, Norichika Asoh, Yukiko Ohara, Shymaa Enany, Haruka Kobayashi, Sohkichi Matsumoto, Konosuke Morimoto

    Frontiers in immunology   14   1222428 - 1222428   2023

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    INTRODUCTION: Controlling pulmonary Mycobacterium avium complex (MAC) disease is difficult because there is no way to know the clinical stage accurately. There have been few attempts to use cell-mediated immunity for diagnosing the stage. The objective of this study was to characterize cytokine profiles of CD4+T and CD19+B cells that recognize various Mycobacterium avium-associated antigens in different clinical stages of MAC. METHODS: A total of 47 MAC patients at different stages based on clinical information (14 before-treatment, 16 on-treatment, and 17 after-treatment) and 17 healthy controls were recruited. Peripheral blood mononuclear cells were cultured with specific antigens (MAV0968, 1160, 1276, and 4925), and the cytokine profiles (IFN-γ, TNF-α, IL-2, IL-10, IL-13, and IL-17) of CD4+/CD3+ and CD19+ cells were analyzed by flow cytometry. RESULTS: The response of Th1 cytokines such as IFN-γ and TNF-α against various antigens was significantly higher in both the on-treatment and after-treatment groups than in the before-treatment group and control (P < 0.01-0.0001 and P < 0.05-0.0001). An analysis of polyfunctional T cells suggested that the presence of IL-2 is closely related to the stage after the start of treatment (P = 0.0309-P < 0.0001) and is involved in memory function. Non-Th1 cytokines, such as IL-10 and IL-17, showed significantly higher responses in the before-treatment group (P < 0.0001 and P < 0.01-0.0001). These responses were not observed with purified protein derivative (PPD). CD19+B cells showed a response similar to that of CD4+T cells. CONCLUSION: There is a characteristic cytokine profile at each clinical stage of MAC.

    DOI： 10.3389/fimmu.2023.1222428

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  • An efficient CRISPR interference-based prediction method for synergistic/additive effects of novel combinations of anti-tuberculosis drugs. International journal

    Noriaki Samukawa, Takehiro Yamaguchi, Yuriko Ozeki, Sohkichi Matsumoto, Masayuki Igarashi, Naoko Kinoshita, Masaki Hatano, Kentaro Tokudome, Shinji Matsunaga, Shuhei Tomita

    Microbiology (Reading, England)   168 ( 12 )   2022.12

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    Tuberculosis (TB) is treated by chemotherapy with multiple anti-TB drugs for a long period, spanning 6 months even in a standard course. In perspective, to prevent the emergence of antimicrobial resistance, novel drugs that act synergistically or additively in combination with major anti-TB drugs and, if possible, shorten the duration of TB therapy are needed. However, their combinatorial effect cannot be predicted until the lead identification phase of the drug development. Clustered regularly interspaced short palindromic repeats interference (CRISPRi) is a powerful genetic tool that enables high-throughput screening of novel drug targets. The development of anti-TB drugs promises to be accelerated by CRISPRi. This study determined whether CRISPRi could be applicable for predictive screening of the combinatorial effect between major anti-TB drugs and an inhibitor of a novel target. In the checkerboard assay, isoniazid killed Mycobacterium smegmatis synergistically or additively in combinations with rifampicin or ethambutol, respectively. The susceptibility to rifampicin and ethambutol was increased by knockdown of inhA, which encodes a target molecule of isoniazid. Additionally, knockdown of rpoB, which encodes a target molecule of rifampicin, increased the susceptibility to isoniazid and ethambutol, which act synergistically with rifampicin in the checkerboard assay. Moreover, CRISPRi could successfully predict the synergistic action of cyclomarin A, a novel TB drug candidate, with isoniazid or rifampicin. These results demonstrate that CRISPRi is a useful tool not only for drug target exploration but also for screening the combinatorial effects of novel combinations of anti-TB drugs. This study provides a rationale for anti-TB drug development using CRISPRi.

    DOI： 10.1099/mic.0.001285

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  • Lysocin E Targeting Menaquinone in the Membrane of Mycobacterium tuberculosis Is a Promising Lead Compound for Antituberculosis Drugs. International journal

    Geberemichal Geberetsadik, Akane Inaizumi, Akihito Nishiyama, Takehiro Yamaguchi, Hiroshi Hamamoto, Suresh Panthee, Aki Tamaru, Manabu Hayatsu, Yusuke Mizutani, Shaban Amina Kaboso, Mariko Hakamata, Aleksandr Ilinov, Yuriko Ozeki, Yoshitaka Tateishi, Kazuhisa Sekimizu, Sohkichi Matsumoto

    Antimicrobial agents and chemotherapy   66 ( 9 )   e0017122   2022.8

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    Tuberculosis remains a public health crisis and a health security threat. There is an urgent need to develop new antituberculosis drugs with novel modes of action to cure drug-resistant tuberculosis and shorten the chemotherapy period by sterilizing tissues infected with dormant bacteria. Lysocin E is an antibiotic that showed antibacterial activity against Staphylococcus aureus by binding to its menaquinone (commonly known as vitamin K2). Unlike S. aureus, menaquinone is essential in both growing and dormant Mycobacterium tuberculosis. This study aims to evaluate the antituberculosis activities of lysocin E and decipher its mode of action. We show that lysocin E has high in vitro activity against both drug-susceptible and drug-resistant Mycobacterium tuberculosis var. tuberculosis and dormant mycobacteria. Lysocin E is likely bound to menaquinone, causing M. tuberculosis membrane disruption, inhibition of oxygen consumption, and ATP synthesis. Thus, we have concluded that the high antituberculosis activity of lysocin E is attributable to its synergistic effects of membrane disruption and respiratory inhibition. The efficacy of lysocin E against intracellular M. tuberculosis in macrophages was lower than its potent activity against M. tuberculosis in culture medium, probably due to its low ability to penetrate cells, but its efficacy in mice was still superior to that of streptomycin. Our findings indicate that lysocin E is a promising lead compound for the development of a new tuberculosis drug that cures drug-resistant and latent tuberculosis in a shorter period.

    DOI： 10.1128/aac.00171-22

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  • 結核・非結核性抗酸菌感染検出パネル開発

    木田 博, 松本 壮吉, 前倉 亮治

    結核   97 ( 4 )   119 - 119   2022.6

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  • Direct Attachment with Erythrocytes Augments Extracellular Growth of Pathogenic Mycobacteria

    Yukiko Nishiuchi, Yoshitaka Tateishi, Hiroshi Hirano, Yuriko Ozeki, Takehiro Yamaguchi, Mari Miki, Seigo Kitada, Fumito Maruyama, Sohkichi Matsumoto

    Microbiology Spectrum   10 ( 2 )   2022.4

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    Pathogenic mycobacteria, such as Mycobacterium tuberculosis , Mycobacterium avium subsp. hominissuis (MAH), and Mycobacterium intracellulare , cause pulmonary infections as intracellular parasites of lung macrophages and epithelial cells. Here, using histopathological examinations we found that MAH and M. intracellulare colocalized with erythrocytes in lung infection sites.

    DOI： 10.1128/spectrum.02454-21

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  • Long-Term Prognosis and Antimycobacterial Glycolipid Antibody as Biomarker in Mycobacterium avium-intracellulare Complex Pulmonary Disease. International journal

    Ryoji Maekura, Keisuke Miki, Yoshitaka Tateishi, Sohkichi Matsumoto, Seigo Kitada, Mari Miki, Hiroshi Kida

    Microbiology spectrum   10 ( 3 )   e0053022   2022.4

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    Clinical characteristics and outcomes of multidrug chemotherapy have been used as the main prognostic factors for Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) over the last decade; however, no useful prognostic biomarkers have been reported. The aim is to ascertain whether the serum antibody titers could include useful prognostic predictors of MAC-PD. Ninety-four patients with MAC-PD were enrolled and regularly followed up with for more than 5 years or until death. Cox proportional hazard regression and receiver operating characteristic (ROC) curve analyses were used to identify predictors of mortality in this prospective observational study. According to treatment outcomes, 85 patients completed follow-up and were classified into four groups. Seventeen patients (20%) died during follow-up (median, 10.1 years; interquartile range, 8.1 to 12.4 years). All 11 patients with MAC-PD-specific death were included in the 14 patients of the group nonresponsive to the multidrug chemotherapy. They had significantly higher anti-Mycobacterium glycolipid (MBGL) antibody titers than those in the other groups and a significantly (P < 0.0001) poorer survival prognosis. The anti-MBGL antibody titers also served as a negative prognostic factor. A cutoff score of 7, which was calculated by clinical poor prognostic characteristics and anti-MBGL antibody titers, differentiated the nonresponse group and the other groups at baseline (sensitivity, specificity, and area under the curve: 92.9%, 81.7%, and 0.95, respectively). In conclusion, anti-MBGL antibody titers were useful to assess the refractory MAC-PD. The predictions of treatment outcome and mortality become more accurate by using anti-MBGL antibody and clinical poor prognostic characteristics together. IMPORTANCE The natural history of MAC-PD is challenging to predict in immunocompetent patients at diagnosis, and the current multidrug chemotherapy options are not strong enough to eliminate mycobacteria from the lungs. Therefore, the diagnosis of MAC-PD does not necessarily lead to the decision to start chemotherapy. We have also observed refractory patients in clinical practice, who were resistant to multiple-drug chemotherapy and showed persistent excretion of MAC bacilli and progressive worsening of chest radiographic findings until death. We have reported that the measurements of anti-MBGL antibody titers helped assess refractory MAC-PD in this study. Furthermore, the predictions of treatment outcome and mortality become more accurate by using the anti-MBGL antibody in addition to clinical poor prognostic characteristics, which were older age, lower body mass index, the positive results of a smear test for acid-fast bacteria (AFB), and presence of cavitary disease.

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  • Monitoring IgG against Mycobacterium tuberculosis proteins in an Asian elephant cured of tuberculosis that developed from long-term latency. International journal

    Satoshi Ishikawa, Yuriko Ozeki, Satomi Suga, Yasuhiko Mukai, Haruka Kobayashi, Erina Inouchi, Shaban A Kaboso, Gebremichal Gebretsadik, Desak Nyoman Surya Suameitria Dewi, Akihito Nishiyama, Yoshitaka Tateishi, Hayato Takihara, Shujiro Okuda, Shiomi Yoshida, Naoaki Misawa, Sohkichi Matsumoto

    Scientific reports   12 ( 1 )   4310 - 4310   2022.3

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    Tuberculosis (TB) is fatal in elephants, hence protecting elephants from TB is key not only in the conservation of this endangered animal, but also to prevent TB transmission from elephants to humans. Most human TB cases arise from long-term asymptomatic infections. Significant diagnostic challenges remain in the detection of both infection and disease development from latency in elephants due to their huge bodies. In this study, we assessed cryopreserved sera collected for over 16 years, from the first Japanese treatment case of elephant TB. Semi-quantification of IgG levels to 11 proteins showed high detection levels of 3 proteins, namely ESAT6/CFP10, MPB83 and Ag85B. The level of IgG specific to these 3 antigens was measured longitudinally, revealing high and stable ESAT6/CFP10 IgG levels regardless of onset or treatment. Ag85B-specifc IgG levels were largely responsive to onset or treatment, while those of MPB83 showed intermediate responses. These results suggest that ESAT6/CFP10 is immunodominant in both asymptomatic and symptomatic phases, making it useful in the detection of infection. On the other hand, Ag85B has the potential to be a marker for the prediction of disease onset and in the evaluation of treatment effectiveness in elephants.

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  • Identification and functional analysis of a new type of <i>Z,E</i> ‐mixed prenyl reductase from mycobacteria

    Tohru Abe, Mariko Hakamata, Akihito Nishiyama, Yoshitaka Tateishi, Sohkichi Matsumoto, Hisashi Hemmi, Daijiro Ueda, Tsutomu Sato

    The FEBS Journal   2022.3

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    DOI： 10.1111/febs.16412

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  • 抗酸菌の新しいタイプのZ、E混成型プレニル基還元酵素の同定と機能解析(Identification and functional analysis of a new type of Z,E-mixed prenyl reductase from mycobacteria)

    阿部 透, 袴田 真理子, 西山 晃史, 立石 善隆, 松本 壮吉, 邊見 久, 上田 大次郎, 佐藤 努

    日本細菌学雑誌   77 ( 1 )   68 - 68   2022.2

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  • GRIM‐19 is a target of mycobacterial Zn2+ metalloprotease 1 and indispensable for NLRP3 inflammasome activation Reviewed International journal

    Tomomi Kurane, Tetsuro Matsunaga, Tomoaki Ida, Kazuko Sawada, Akira Nishimura, Masayuki Fukui, Masayuki Umemura, Masaaki Nakayama, Naoya Ohara, Sohkichi Matsumoto, Takaaki Akaike, Goro Matsuzaki, Giichi Takaesu

    The FASEB Journal   36 ( 1 )   e22096   2022.1

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    Tuberculosis is a communicable disease caused by Mycobacterium tuberculosis which primarily infects macrophages and establishes intracellular parasitism. A mycobacterial virulence factor Zn2+ metalloprotease 1 (Zmp1) is known to suppress interleukin (IL)-1β production by inhibiting caspase-1 resulting in phagosome maturation arrest. However, the molecular mechanism of caspase-1 inhibition by Zmp1 is still elusive. Here, we identified GRIM-19 (also known as NDUFA13), an essential subunit of mitochondrial respiratory chain complex I, as a novel Zmp1-binding protein. Using the CRISPR/Cas9 system, we generated GRIM-19 knockout murine macrophage cell line J774.1 and found that GRIM-19 is essential for IL-1β production during mycobacterial infection as well as in response to NLRP3 inflammasome-activating stimuli such as extracellular ATP or nigericin. We also found that GRIM-19 is required for the generation of mitochondrial reactive oxygen species and NLRP3-dependent activation of caspase-1. Loss of GRIM-19 or forced expression of Zmp1 resulted in a decrease in mitochondrial membrane potential. Our study revealed a previously unrecognized role of GRIM-19 as an essential regulator of NLRP3 inflammasome and a molecular mechanism underlying Zmp1-mediated suppression of IL-1β production during mycobacterial infection.

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  • Extracellular DNA of slow growers of mycobacteria and its contribution to biofilm formation and drug tolerance International journal

    Aleksandr Ilinov, Akihito Nishiyama, Hiroki Namba, Yukari Fukushima, Hayato Takihara, Chie Nakajima, Anna Savitskaya, Gebremichal Gebretsadik, Mariko Hakamata, Yuriko Ozeki, Yoshitaka Tateishi, Shujiro Okuda, Yasuhiko Suzuki, Yuri S. Vinnik, Sohkichi Matsumoto

    Scientific Reports   11 ( 1 )   10953 - 10953   2021.12

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    <title>Abstract</title>DNA is basically an intracellular molecule that stores genetic information and carries instructions for growth and reproduction in all cellular organisms. However, in some bacteria, DNA has additional roles outside the cells as extracellular DNA (eDNA), which is an essential component of biofilm formation and hence antibiotic tolerance. Mycobacteria include life-threating human pathogens, most of which are slow growers. However, little is known about the nature of pathogenic mycobacteria’s eDNA. Here we found that eDNA is present in slow-growing mycobacterial pathogens, such as <italic>Mycobacterium tuberculosis</italic>, <italic>M. intracellulare</italic>, and <italic>M. avium</italic> at exponential growth phase. In contrast, eDNA is little in all tested rapid-growing mycobacteria. The physiological impact of disrupted eDNA on slow-growing mycobacteria include reduced pellicle formation, floating biofilm, and enhanced susceptibility to isoniazid and amikacin. Isolation and sequencing of eDNA revealed that it is identical to the genomic DNA in <italic>M. tuberculosis</italic> and <italic>M. intracellulare</italic>. In contrast, accumulation of phage DNA in eDNA of <italic>M. avium</italic>, suggests that the DNA released differs among mycobacterial species. Our data show important functions of eDNA necessary for biofilm formation and drug tolerance in slow-growing mycobacteria.

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  • Comparative genomic analysis of Mycobacterium intracellulare: implications for clinical taxonomic classification in pulmonary Mycobacterium avium-intracellulare complex disease International journal

    Yoshitaka Tateishi, Yuriko Ozeki, Akihito Nishiyama, Mari Miki, Ryoji Maekura, Yukari Fukushima, Chie Nakajima, Yasuhiko Suzuki, Sohkichi Matsumoto

    BMC Microbiology   21 ( 1 )   103 - 103   2021.12

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    <title>Abstract</title><sec>
    <title>Background</title>
    <italic>Mycobacterium intracellulare</italic> is a representative etiological agent of emerging pulmonary <italic>M. avium-intracellulare</italic> complex disease in the industrialized countries worldwide. The recent genome sequencing of clinical strains isolated from pulmonary <italic>M. avium-intracellulare</italic> complex disease has provided insight into the genomic characteristics of pathogenic mycobacteria, especially for <italic>M. avium</italic>; however, the genomic characteristics of <italic>M. intracellulare</italic> remain to be elucidated.


    </sec><sec>
    <title>Results</title>
    In this study, we performed comparative genomic analysis of 55 <italic>M. intracellulare</italic> and related strains such as <italic>M. paraintracellulare</italic> (MP), <italic>M. indicus pranii</italic> (MIP) and <italic>M. yonogonense</italic>. Based on the average nucleotide identity, the clinical <italic>M. intracellulare</italic> strains were phylogenetically grouped in two clusters: (1) the typical <italic>M. intracellulare</italic> (TMI) group, including ATCC13950 and virulent M.i.27 and M.i.198 that we previously reported, and (2) the MP-MIP group. The alignment of the genomic regions was mostly preserved between groups. Plasmids were identified between groups and subgroups, including a plasmid common among some strains of the M.i.27 subgroup. Several genomic regions including those encoding factors involved in lipid metabolism (e.g., <italic>fadE3</italic>, <italic>fadE33</italic>), transporters (e.g., <italic>mce3</italic>), and type VII secretion system (genes of ESX-2 system) were shown to be hypermutated in the clinical strains. <italic>M. intracellulare</italic> was shown to be pan-genomic at the species and subspecies levels. The <italic>mce</italic> genes were specific to particular subspecies, suggesting that these genes may be helpful in discriminating virulence phenotypes between subspecies.


    </sec><sec>
    <title>Conclusions</title>
    Our data suggest that genomic diversity among <italic>M. intracellulare</italic>, <italic>M. paraintracellulare</italic>, <italic>M. indicus pranii</italic> and <italic>M. yonogonense</italic> remains at the subspecies or genovar levels and does not reach the species level. Genetic components such as <italic>mce</italic> genes revealed by the comparative genomic analysis could be the novel focus for further insight into the mechanism of human pathogenesis for <italic>M. intracellulare</italic> and related strains.


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    DOI： 10.1186/s12866-021-02163-9

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  • Microbiome in sputum as a potential biomarker of chronicity in pulmonary resistant to rifampicin-tuberculosis and multidrug-resistant-tuberculosis patients.

    Wiqoyah N, Mertaniasih NM, Artama WT, Matsumoto S

    2021.7

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  • Evaluation of a booster tuberculosis vaccine containing mycobacterial DNA-binding protein 1 and CpG oligodeoxynucleotide G9.1 using a Guinea pig model that elicits immunity to Bacillus Calmette–Guérin International journal

    Jun-ichi Maeyama, Sumiko Iho, Fumiko Suzuki, Daisuke Hayashi, Toshiko Yamamoto, Toshio Yamazaki, Yoshitaka Goto, Yuriko Ozeki, Sohkichi Matsumoto, Saburo Yamamoto

    Tuberculosis   128   102067 - 102067   2021.5

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    Tuberculosis is a major threat to global health and its increased incidence in adolescents as well as onset in the elderly presents a serious problem. One strategy to control tuberculosis involves taking advantage of Bacillus Calmette-Guérin's (BCG) superior effects on childhood tuberculosis. Accordingly, here we aimed to develop a booster vaccine for adults who received the BCG vaccine during early childhood. Therefore, we first devised a system to assess the efficacy of a candidate booster vaccine. Specifically, variant strain BCG-II, a minor component of BCG-Tokyo strain, which elicits weak immunity, was administered to guinea pigs. Vaccine-induced immunity and protection against Mycobacterium tuberculosis (Mtb) infection were evaluated using skin delayed-type hypersensitivity (DTH) and Mtb colony forming unit counts in organs, respectively. Candidate booster vaccine containing the mycobacterial DNA-binding protein 1 (MDP1) as antigen and CpG oligodeoxynucleotide G9.1 as adjuvant increased T-bet expression and IFN-γ production in human peripheral blood mononuclear cells. Intradermal administration of MDP1 or MDP1 and G9.1 to unimmunized guinea pigs produced DTH on MDP1-inoculated skin. Boosting BCG-II-primed guinea pigs with this protocol effectively enhanced DTH against MDP1 and protection against Mtb infection, particularly when combined with G9.1. The candidate vaccine may contribute to efforts to prevent tuberculosis.

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  • 早期発症者と長期潜伏後発症者より分離した結核菌北京株のゲノム変異解析

    袴田 真理子, 瀧原 速仁, 岩本 朋忠, 田丸 亜貴, 尾関 百合子, 西山 晃史, 立石 善隆, 菊地 利明, 奥田 修二郎, 松本 壮吉

    結核   96 ( 3 )   83 - 86   2021.5

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  • 病原因子と生態防御(感染モデル・寄生・免疫・ワクチン)/病原体と感染症 組織透明化/3次元イメージング「CUBIC」による抗酸菌感染の生体内モニタリング

    袴田 真理子, 井内 絵梨奈, 横山 晃, 尾関 百合子, 西山 晃史, 立石 善隆, 大橋 璃子, 菊地 利明, 田井中 一貴, 松本 壮吉

    日本細菌学雑誌   76 ( 1 )   59 - 59   2021.2

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  • 四半世紀に及んだ腸管出血性大腸菌感染症の戦いと未来 感染症ミューズ細胞治療の挑戦(Quarter century battle against EHEC infectious disease; Muse cell therapy challenge on infectious diseases)

    藤井 潤, 出澤 真理, 尾鶴 亮, 若尾 昌平, 辻 高寛, 松葉 隆司, 黒沢 洋一, 大原 直也, 松本 壮吉, 安田 香央里, 飯野 守男

    日本細菌学雑誌   76 ( 1 )   126 - 126   2021.2

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  • 低酸素環境と疾患(がん、感染症)の分子論 低酸素休眠抗酸菌の主要タンパク質Mycobacterial DNA-binding protein 1(My cobacterial DNA-binding protein 1, a major protein in hypoxic dormant mycobacteria)

    西山 晃史, 古寺 哲幸, 清水 将裕, Savitskaya Anna, Enany Shymaa, 真柳 浩太, 山口 雄大, 尾関 百合子, 立石 善隆, 松本 壮吉

    日本細菌学雑誌   76 ( 1 )   57 - 57   2021.2

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  • 世界結核デーにちなんで、世界の結核・抗酸菌症研究のこれまでと今 結核菌北京株のゲノム解析と組織透明化/3次元イメージング「CUBIC」による抗酸菌感染の生体内モニタリング

    袴田 真理子, 瀧原 速仁, 尾関 百合子, 西山 晃史, 立石 善隆, 大橋 璃子, 奥田 修二郎, 田井中 一貴, 菊地 利明, 松本 壮吉

    日本細菌学雑誌   76 ( 1 )   65 - 65   2021.2

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  • Differential Protein Expression in Exponential and Stationary Growth Phases of Mycobacterium avium subsp. hominissuis 104 International journal

    Shymaa Enany, Manabu Ato, Sohkichi Matsumoto

    Molecules   26 ( 2 )   305 - 305   2021.1

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    Mycobacterium avium complex (MAC) is the most common non-tuberculous mycobacterium (NTM) and causes different types of pulmonary diseases. While genomic and transcriptomic analysis of Mycobacterium avium 104 (M. avium 104) has been extensive, little is known about the proteomics of M. avium 104. We utilized proteomics technology to analyze the changes in the whole proteome of M. avium 104 during exponential and stationary growth phases. We found 12 dys-regulated proteins; the up-regulated protein hits in the stationary phase were involved in aminopeptidase, choline dehydrogenase, oxidoreductase, and ATP binding, while the down-regulated proteins in the stationary phase were acetyl-CoA acetyltransferase, universal stress protein, catalase peroxidase, and elongation factor (Tu). The differently expressed proteins between exponential and stationary phases were implicated in metabolism and stress response, pointing to the functional adaptation of the cells to the environment. Proteomic analysis in different growth phases could participate in understanding the course of infection, the mechanisms of virulence, the means of survival, and the possible targets for treatment.

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  • Correction: Significance of a histone-like protein with its native structure for the diagnosis of asymptomatic tuberculosis. International journal

    Yukiko Ohara, Yuriko Ozeki, Yoshitaka Tateishi, Tsukasa Mashima, Fumio Arisaka, Yasuo Tsunaka, Yoshie Fujiwara, Akihito Nishiyama, Yutaka Yoshida, Kengo Kitadokoro, Haruka Kobayashi, Yukihiro Kaneko, Ichiro Nakagawa, Ryoji Maekura, Saburo Yamamoto, Masato Katahira, Sohkichi Matsumoto

    PloS one   16 ( 8 )   e0256946   2021

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    [This corrects the article DOI: 10.1371/journal.pone.0204160.].

    DOI： 10.1371/journal.pone.0256946

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  • Genome-wide identification of essential genes in Mycobacterium intracellulare by transposon sequencing — Implication for metabolic remodeling

    Yoshitaka Tateishi, Yusuke Minato, Anthony D. Baughn, Hiroaki Ohnishi, Akihito Nishiyama, Yuriko Ozeki, Sohkichi Matsumoto

    Scientific Reports   10 ( 1 )   2020.12

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    <title>Abstract</title>The global incidence of the human nontuberculous mycobacteria (NTM) disease is rapidly increasing. However, knowledge of gene essentiality under optimal growth conditions and conditions relevant to the natural ecology of NTM, such as hypoxia, is lacking. In this study, we utilized transposon sequencing to comprehensively identify genes essential for growth in <italic>Mycobacterium intracellulare</italic>. Of 5126 genes of <italic>M. intracellulare</italic> ATCC13950, 506 genes were identified as essential genes, of which 280 and 158 genes were shared with essential genes of <italic>M. tuberculosis</italic> and <italic>M. marinum</italic>, respectively. The shared genes included target genes of existing antituberculous drugs including SQ109, which targets the trehalose monomycolate transporter MmpL3. From 175 genes showing decreased fitness as conditionally essential under hypoxia, preferential carbohydrate metabolism including gluconeogenesis, glyoxylate cycle and succinate production was suggested under hypoxia. Virulence-associated genes including proteasome system and mycothiol redox system were also identified as conditionally essential under hypoxia, which was further supported by the higher effective suppression of bacterial growth under hypoxia compared to aerobic conditions in the presence of these inhibitors. This study has comprehensively identified functions essential for growth of <italic>M. intracellulare</italic> under conditions relevant to the host environment. These findings provide critical functional genomic information for drug discovery.

    DOI： 10.1038/s41598-020-62287-2

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  • Higher genome mutation rates of Beijing lineage of Mycobacterium tuberculosis during human infection International journal

    Mariko Hakamata, Hayato Takihara, Tomotada Iwamoto, Aki Tamaru, Atsushi Hashimoto, Takahiro Tanaka, Shaban A. Kaboso, Gebremichal Gebretsadik, Aleksandr Ilinov, Akira Yokoyama, Yuriko Ozeki, Akihito Nishiyama, Yoshitaka Tateishi, Hiroshi Moro, Toshiaki Kikuchi, Shujiro Okuda, Sohkichi Matsumoto

    Scientific Reports   10 ( 1 )   17997 - 17997   2020.12

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    <title>Abstract</title>
    <italic>Mycobacterium tuberculosis</italic> (<italic>Mtb</italic>) strains of Beijing lineage have caused great concern because of their rapid emergence of drug resistance and worldwide spread. DNA mutation rates that reflect evolutional adaptation to host responses and the appearance of drug resistance have not been elucidated in human-infected Beijing strains. We tracked and obtained an original <italic>Mtb</italic> isolate of Beijing lineage from the 1999 tuberculosis outbreak in Japan, as well as five other isolates that spread in humans, and two isolates from the patient caused recurrence. Three isolates were from patients who developed TB within one year after infection (rapid-progressor, RP), and the other three isolates were from those who developed TB more than one year after infection (slow-progressor, SP). We sequenced genomes of these isolates and analyzed the propensity and rate of genomic mutations. Generation time versus mutation rate curves were significantly higher for RP. The ratio of oxidative versus non-oxidation damages induced mutations was higher in SP than RP, suggesting that persistent <italic>Mtb</italic> are exposed to oxidative stress in the latent state. Our data thus demonstrates that higher mutation rates of <italic>Mtb</italic> Beijing strains during human infection is likely to account for the higher adaptability and an emergence ratio of drug resistance.

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  • 早期発症者と長期潜伏後発症者より分離した結核菌北京株のゲノム変異解析

    袴田 真理子, 瀧原 速仁, 岩本 朋忠, 田丸 亜貴, 尾関 百合子, 西山 晃史, 菊地 利明, 奥田 修二郎, 松本 壮吉

    結核   95 ( 5 )   115 - 115   2020.9

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  • 尿プロテオミクスによる肺MAC症のバイオマーカー探索

    横山 晃, 平尾 嘉利, 尾関 百合子, 西山 晃史, 立石 善隆, 桑原 克弘, 菊地 利明, 山本 格, 松本 壮吉

    結核   95 ( 5 )   146 - 146   2020.9

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  • Nontuberculous Mycobacterial Lung Disease Complicated by Radiological Pleuroparenchymal Fibroelastosis Pattern

    S. Okamori, T. Asakura, K. Furuuchi, M. Yagi, T. Matsumoto, K. Yagi, I. Hase, H. Kamata, K. Fujiwara, M. Ishii, K. Ogawa, K. Morimoto, M. Fujita, Y. Sasaki, N. Hasegawa, O.N.-J. Nontuberculous Mycobacteriosis-Japan Research Cons

    C53. GLOBAL EXPERIENCES IN TB AND NTM CARE   2020.5

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    DOI： 10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a5429

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  • 【結核を考える-肺結核を中心に】結核の分子疫学検査

    袴田 真理子, 茂呂 寛, 松本 壮吉, 菊地 利明

    呼吸器内科   37 ( 5 )   465 - 470   2020.5

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  • 抗酸菌のバイオフィルム形成と休眠時遺伝子発現比較

    西内 由紀子, 大田 篤, 矢野 大和, 岩本 朋忠, 阿戸 学, 松本 壮吉, 大原 直也, 丸山 史人

    BACTERIAL ADHERENCE & BIOFILM   33   49 - 52   2020.5

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  • Adduct Formation of Delamanid with NAD in Mycobacteria

    Mikayo Hayashi, Akihito Nishiyama, Ryuki Kitamoto, Yoshitaka Tateishi, Mayuko Osada-Oka, Yukiko Nishiuchi, Shaban A. Kaboso, Xiuhao Chen, Mamoru Fujiwara, Yusuke Inoue, Yoshikazu Kawano, Masanori Kawasaki, Tohru Abe, Tsutomu Sato, Kentaro Kaneko, Kimiko Itoh, Sohkichi Matsumoto, Makoto Matsumoto

    Antimicrobial Agents and Chemotherapy   64 ( 5 )   2020.4

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    Delamanid (DLM), a nitro-dihydroimidazooxazole derivative currently approved for pulmonary multidrug-resistant tuberculosis (TB) therapy, is a prodrug activated by mycobacterial 7,8-didemethyl-8-hydroxy 5-deazaflavin electron transfer coenzyme (F
    <sub>420</sub>
    )-dependent nitroreductase (Ddn). Despite inhibiting the biosynthesis of a subclass of mycolic acids, the active DLM metabolite remained unknown. Comparative liquid chromatography-mass spectrometry (LC-MS) analysis of DLM metabolites revealed covalent binding of reduced DLM with a nicotinamide ring of NAD derivatives (oxidized form) in DLM-treated
    <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>
    var.

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  • Adduct Formation of Delamanid with NAD in Mycobacteria Reviewed

    Mikayo Hayashi, Akihito Nishiyama, Ryuki Kitamoto, Yoshitaka Tateishi, Mayuko Osada-Oka, Yukiko Nishiuchi, Shaban A. Kaboso, Xiuhao Chen, Mamoru Fujiwara, Yusuke Inoue, Yoshikazu Kawano, Masanori Kawasaki, Tohru Abe, Tsutomu Sato, Kentaro Kaneko, Kimiko Itoh, Sohkichi Matsumoto, Makoto Matsumoto

    Antimicrobial Agents and Chemotherapy   64 ( 5 )   2020.4

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    <title>ABSTRACT</title>
    Delamanid (DLM), a nitro-dihydroimidazooxazole derivative currently approved for pulmonary multidrug-resistant tuberculosis (TB) therapy, is a prodrug activated by mycobacterial 7,8-didemethyl-8-hydroxy 5-deazaflavin electron transfer coenzyme (F<sub>420</sub>)-dependent nitroreductase (Ddn). Despite inhibiting the biosynthesis of a subclass of mycolic acids, the active DLM metabolite remained unknown. Comparative liquid chromatography-mass spectrometry (LC-MS) analysis of DLM metabolites revealed covalent binding of reduced DLM with a nicotinamide ring of NAD derivatives (oxidized form) in DLM-treated <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> var. Bacille de Calmette et Guérin. Isoniazid-resistant mutations in the type II NADH dehydrogenase gene (<italic>ndh</italic>) showed a higher intracellular NADH/NAD ratio and cross-resistance to DLM, which were restored by complementation of the mutants with wild-type <italic>ndh</italic>. Our data demonstrated for the first time the adduct formation of reduced DLM with NAD in mycobacterial cells and its importance in the action of DLM.

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  • Rescue from Stx2-Producing E. coli-Associated Encephalopathy by Intravenous Injection of Muse Cells in NOD-SCID Mice

    Ryo Ozuru, Shohei Wakao, Takahiro Tsuji, Naoya Ohara, Takashi Matsuba, Muhammad Y. Amuran, Junko Isobe, Morio Iino, Naoki Nishida, Sari Matsumoto, Kimiharu Iwadate, Noriko Konishi, Kaori Yasuda, Kosuke Tashiro, Misato Hida, Arisato Yadoiwa, Shinsuke Kato, Eijiro Yamashita, Sohkichi Matsumoto, Yoichi Kurozawa, Mari Dezawa, Jun Fujii

    Molecular Therapy   28 ( 1 )   100 - 118   2020.1

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    DOI： 10.1016/j.ymthe.2019.09.023

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  • 病原性抗酸菌における細胞外DNAの存在と抗酸菌の生理におけるその役割(Existence of extracellular DNA in pathogenic mycobacteria and its role in mycobacterial physiology)

    イリノフ・アレクサンドル, シャバン・アミナ, 袴田 真理子, 西山 晃史, 尾関 百合子, 福島 由華里, 中島 千絵, 立石 善隆, 鈴木 定彦, 松本 壮吉

    日本細菌学雑誌   75 ( 1 )   74 - 74   2020.1

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  • 早期発症者と長期潜伏後発症者より分離した結核菌北京株のゲノム変異についての解析

    袴田 真理子, 瀧原 速仁, 岩本 朋忠, 田丸 亜貴, 尾関 百合子, 西山 晃史, 立石 善隆, 菊地 利明, 奥田 修二郎, 松本 壮吉

    日本細菌学雑誌   75 ( 1 )   129 - 129   2020.1

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  • 抗酸菌症治療薬を目指した標的蛋白質の発現と精製

    大原 由貴子, 小林 悠, 尾関 百合子, 西山 晃史, 立石 善隆, 奥田 修二郎, 神谷 重樹, 北所 健悟, 松本 壮吉

    日本細菌学雑誌   75 ( 1 )   74 - 74   2020.1

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  • 抗酸菌ヒストン様タンパク質の天然変性領域依存的なDNA凝集作用

    西山 晃史, 成田 知恕, 古寺 哲幸, 小林 瑶子, 武藤 寛亨, 渡辺 順也, 大原 直也, 尾関 百合子, 立石 善隆, 松本 壮吉

    日本細菌学雑誌   75 ( 1 )   132 - 132   2020.1

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  • MDP1はM.tuberculosis var BCG株の生存を確固とするための代謝と複製を調節する(MDP1 regulates metabolism and replication ensuring the survival of M. tuberculosis var BCG)

    シャバン・アミナ, 西山 晃史, 立石 善隆, 山口 雄大, 西内 由紀子, 瀧原 速仁, 奥田 修二郎, 松本 壮吉

    日本細菌学雑誌   75 ( 1 )   88 - 88   2020.1

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  • 尿ウロテオミクスによる肺MAC症のバイオマーカー探索

    横山 晃, 平尾 嘉利, 尾関 百合子, 西山 晃史, 立石 善隆, 山本 格, 松本 壮吉

    日本細菌学雑誌   75 ( 1 )   117 - 117   2020.1

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  • Nutritional status positively impacts humoral immunity against its Mycobacterium tuberculosis, disease progression, and vaccine development. Reviewed International journal

    Mamiko Niki, Takashi Yoshiyama, Hideaki Nagai, Yuji Miyamoto, Makoto Niki, Ken-Ichi Oinuma, Taishi Tsubouchi, Yukihiro Kaneko, Sohkichi Matsumoto, Yuka Sasaki, Yoshihiko Hoshino

    PloS one   15 ( 8 )   e0237062   2020

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    Nutritional status contributes to the regulation of immune responses against pathogens, and malnutrition has been considered as a risk factor for tuberculosis (TB). Mycobacterium tuberculosis (Mtb), the causative agent of TB, can modulate host lipid metabolism and induce lipid accumulation in macrophages, where the bacilli adopt a dormant phenotype. In addition, serum lipid components play dual roles in the regulation of and protection from Mtb infection. We analyzed the relationship between nutritional status and the humoral immune response in TB patients. We found that serum HDL levels are positively correlated with the serum IgA specific for Mtb antigens. Analysis of the relationship between serum nutritional parameters and clinical parameters in TB patients showed that serum albumin and CRP levels were negatively correlated before treatment. We also observed reduced serum LDL levels in TB patients following treatment. These findings may provide insight into the role of serum lipids in host immune responses against Mtb infection. Furthermore, improving the nutritional status may enhance vaccination efficacy.

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  • Characteristic profile of antibody responses to PPD, ESAT-6, and CFP-10 of Mycobacterium tuberculosis in pulmonary tuberculosis suspected cases in Surabaya, Indonesia

    Desak Nyoman Surya Suameitria Dewi, Ni Made Mertaniasih, Soedarsono, Yuriko Ozeki, Wayan Tunas Artama, Fihiruddin, Mamiko Niki, Yoshitaka Tateishi, Manabu Ato, Sohkichi Matsumoto

    The Brazilian Journal of Infectious Diseases   23 ( 4 )   246 - 253   2019.7

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    DOI： 10.1016/j.bjid.2019.07.001

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  • Metabolic adaptation to glycolysis is a basic defense mechanism of macrophages for Mycobacterium tuberculosis infection Reviewed

    Mayuko Osada-Oka, Nobuhito Goda, Hiroyuki Saiga, Masahiro Yamamoto, Kiyoshi Takeda, Yuriko Ozeki, Takehiro Yamaguchi, Tomoyoshi Soga, Yu Tateishi, Katsuyuki Miura, Daisuke Okuzaki, Kazuo Kobayashi, Sohkichi Matsumoto

    INTERNATIONAL IMMUNOLOGY   31 ( 12 )   781 - 793   2019.6

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    DOI： 10.1093/intimm/dxz048

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  • 抗酸菌のバイオフィルム形成と休眠時遺伝子発現比較

    西内 由紀子, 大田 篤, 矢野 大和, 岩本 朋忠, 阿戸 学, 松本 壮吉, 大原 直也, 丸山 史人

    日本バイオフィルム学会学術集会プログラム・抄録集   33回   24 - 25   2019.6

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  • バイオフィルム形成条件における遺伝子発現解析

    西内 由紀子, 大田 篤, 岩本 朋忠, 阿戸 学, 松本 壮吉, 丸山 史人

    BACTERIAL ADHERENCE & BIOFILM   32   37 - 42   2019.5

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  • Serum antibody profiles in individuals with latent Mycobacterium tuberculosis infection. Reviewed International journal

    Maekura R, Kitada S, Osada-Oka M, Tateishi Y, Ozeki Y, Fujicawa T, Miki M, Jyunnko O, Mori M, Matsumoto S

    Microbiology and immunology   63 ( 3-4 )   130 - 138   2019.3

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    One-third of the world's humans has latent tuberculosis infection (LTBI), representing a large pool of potentially active TB. Recent LTBI carries a higher risk of disease progression than remote LTBI. Recent studies suggest important roles of antibodies in TB pathology, prompting us to investigate serum antibody profiles in a cohort with LTBI. In this single-center prospective observational study, we analyzed IgG-antibody concentrations against five major Mycobacterium tuberculosis (Mtb) antigens (including 6 kDa early secretory antigenic target (ESAT6), CFP10, and antigen 85A, which are expressed mainly in the growth phase; and mycobacterial DNA-binding protein 1 (MDP1) and alpha-crystallin like protein (Acr), which are expressed in the dormant phases) in individuals with recent (n=13) or remote (n=12) LTBI, no Mtb infection (n=19), or active TB (n=15). Antibody titers against ESAT6 and MDP1 were significantly higher in individuals with recent LTBI than in those with no Mtb infection or remote LTBI. All pairwise antibody titers against these five major antigens were significantly correlated throughout the stages of Mtb infection. Five individuals with recent LTBI had significantly higher antibody titers against ESAT6 (P = 0.03), Ag85A (P = 0.048), Acr (P = 0.057), and MDP1 (P = 0.0001) than in individuals with remote LTBI; they were also outside the normal range (+2 SDs). One of these individuals was diagnosed with active pulmonary TB at 18-month follow-up examination. These findings indicated that concentrations of antibodies against both multiplying and dormant Mtb are higher in recent LTBI and that individuals with markedly higher antibody titers may be appropriate candidates for prophylactic therapy.

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  • 非結核性抗酸菌のバイオフィルム形成条件における遺伝子発現解析(Detection of Differential Gene Expression in Biofilm-Forming Mycobacterium avium subsp. hominissuis)

    西内 由紀子, 大田 篤, 岩本 朋忠, 阿戸 学, 松本 壮吉, 大原 直也, 丸山 史人

    日本細菌学雑誌   74 ( 1 )   109 - 109   2019.3

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  • 菌の休眠と覚醒のメカニズムと意義 休眠中のマイコバクテリアの主要タンパク質であるマイコバクテリアのヒストン様タンパク質MDP1の機能(The functions of mycobacterial histone-like protein MDP1, a major protein in dormant mycobacteria)

    西山 晃史, Savitskaya Anna, 山口 雄大, 大原 直也, 成田 知恕, 古寺 哲幸, 尾関 百合子, 立石 善隆, 松本 壮吉

    日本細菌学雑誌   74 ( 1 )   8 - 8   2019.3

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  • CD4+ T Responses Other Than Th1 Type Are Preferentially Induced by Latency-Associated Antigens in the State of Latent Mycobacterium tuberculosis Infection. Reviewed International journal

    Yoshiro Yamashita, Toshiyuki Oe, Kenji Kawakami, Mayuko Osada-Oka, Yuriko Ozeki, Kazutaka Terahara, Ikkoh Yasuda, Tansy Edwards, Takeshi Tanaka, Yasuko Tsunetsugu-Yokota, Sohkichi Matsumoto, Koya Ariyoshi

    Frontiers in immunology   10   2807 - 2807   2019

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    Mycobacterium tuberculosis (M. tuberculosis) produces a diverse range of antigenic proteins in its dormant phase. The cytokine profiles of CD4+ T cell responses, especially subsets other than Th1 type (non-Th1 type), against these latency-associated M. tuberculosis antigens such as α-crystallin (Acr), heparin-binding hemagglutinin (HBHA), and mycobacterial DNA-binding protein 1 (MDP-1) remain elusive in relation to the clinical stage of M. tuberculosis infection. In the present study, peripheral blood mononuclear cells (PBMCs) collected from different stages of M. tuberculosis-infected cases and control PBMCs were stimulated with these antigens and ESAT-6/CFP-10. Cytokine profiles of CD4+ T cells were evaluated by intracellular cytokine staining using multicolor flow cytometry. Our results demonstrate that Th1 cytokine responses were predominant after TB onset independent of the type of antigen stimulation. On the contrary, non-Th1 cytokine responses were preferentially induced by latency-associated M. tuberculosis antigens, specifically IL-10 response against Acr in latent M. tuberculosis infection. From these results, we surmise a shift in the CD4+ T cell response from mixed non-Th1 to Th1 dominant type during TB progression.

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  • C-terminal intrinsically disordered region-dependent organization of the mycobacterial genome by a histone-like protein Reviewed

    Anna Savitskaya, Akihito Nishiyama, Takehiro Yamaguchi, Yoshitaka Tateishi, Yuriko Ozeki, Masaaki Nameta, Tomohiro Kon, Shaban A. Kaboso, Naoya Ohara, Olga V. Peryanova, Sohkichi Matsumoto

    Scientific Reports   8 ( 1 )   8197   2018.12

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    DOI： 10.1038/s41598-018-26463-9

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  • High-density lipoprotein suppresses tumor necrosis factor alpha production by mycobacteria-infected human macrophages Reviewed

    Manabu Inoue, Mamiko Niki, Yuriko Ozeki, Sachiyo Nagi, Evans Asena Chadeka, Takehiro Yamaguchi, Mayuko Osada-Oka, Kenji Ono, Tetsuya Oda, Faith Mwende, Yukihiro Kaneko, Makoto Matsumoto, Satoshi Kaneko, Yoshio Ichinose, Sammy M. Njenga, Shinjiro Hamano, Sohkichi Matsumoto

    Scientific Reports   8 ( 1 )   6736   2018.12

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    DOI： 10.1038/s41598-018-24233-1

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  • Longitudinal Evaluation of Humoral Immunity and Bacterial and Clinical Parameters Reveals That Antigen-Specific Antibodies Suppress Inflammatory Responses in Active Tuberculosis Patients. Reviewed International journal

    Mamiko Niki, Takashi Yoshiyama, Yuji Miyamoto, Masao Okumura, Makoto Niki, Ken-Ichi Oinuma, Yukihiro Kaneko, Sohkichi Matsumoto, Yuka Sasaki, Hideo Ogata, Hajime Goto, Shoji Kudoh, Yoshihiko Hoshino

    Journal of immunology research   2018   4928757 - 4928757   2018

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    A novel tuberculosis vaccine to replace BCG has long been desired. However, recent vaccine trials focused on cell-mediated immunity have failed to produce promising results. It is worth noting that most commercially available successful vaccines rely on humoral immunity. To establish a basic understanding of humoral immunity against tuberculosis, we analyzed and evaluated longitudinal levels and avidity of immunoglobulin to various tuberculosis antigens compared with bacterial and clinical parameters during treatment. We found that levels of IgG antibodies against HrpA and HBHA prior to treatment exhibited a positive correlation with bacterial burden. Analysis of changes in CRP during treatment revealed an association with high levels of specific IgG and IgA antibodies against mycobacterial antigens. Levels of CRP prior to treatment were negatively associated with IgG avidity to CFP-10 and MDP1 and IgA avidity to HrpA, while IgA avidity to MDP1 and Acr exhibited a negative correlation with CRP levels after 60 days of treatment. These results may provide insight for the development of a novel tuberculosis (TB) vaccine candidate to induce protective humoral immunity against tuberculosis.

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  • Significance of a histone-like protein with its native structure for the diagnosis of asymptomatic tuberculosis. Reviewed International journal

    Ohara Y, Ozeki Y, Tateishi Y, Mashima T, Arisaka F, Tsunaka Y, Fujiwara Y, Nishiyama A, Yoshida Y, Kitadokoro K, Kobayashi H, Kaneko Y, Nakagawa I, Maekura R, Yamamoto S, Katahira M, Matsumoto S

    PloS one   13 ( 10 )   e0204160   2018

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    Tuberculosis causes the highest mortality among all single infections. Asymptomatic tuberculosis, afflicting one third of the global human population, is the major source as 5-10% of asymptomatic cases develop active tuberculosis during their lifetime. Thus it is one of important issues to develop diagnostic tools for accurately detecting asymptomatic infection. Mycobacterial DNA-binding protein 1 (MDP1) is a major protein in persistent Mycobacterium tuberculosis and has potential for diagnostic use in detecting asymptomatic infection. However, a previous ELISA-based study revealed a specificity problem; IgGs against MDP1 were detected in both M. tuberculosis-infected and uninfected individuals. Although the tertiary structures of an antigen are known to influence antibody recognition, the MDP1 structural details have not yet been investigated. The N-terminal half of MDP1, homologous to bacterial histone-like protein HU, is predicted to be responsible for DNA-binding, while the C-terminal half is assumed as totally intrinsically disordered regions. To clarify the relationship between the MDP1 tertiary structure and IgG recognition, we refined the purification method, which allow us to obtain a recombinant protein with the predicted structure. Furthermore, we showed that an IgG-ELISA using MDP1 purified by our refined method is indeed useful in the detection of asymptomatic tuberculosis.

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  • Spatial distribution and risk factors of Schistosoma haematobium and hookworm infections among schoolchildren in Kwale, Kenya Reviewed

    Evans Asena Chadeka, Sachiyo Nagi, Toshihiko Sunahara, Ngetich Benard Cheruiyot, Felix Bahati, Yuriko Ozeki, Manabu Inoue, Mayuko Osada-Oka, Mayuko Okabe, Yukio Hirayama, Mwatasa Changoma, Keishi Adachi, Faith Mwende, Mihoko Kikuchi, Risa Nakamura, Yombo Dan Justin Kalenda, Satoshi Kaneko, Kenji Hirayama, Masaaki Shimada, Yoshio Ichinose, Sammy M. Njenga, Sohkichi Matsumoto, Shinjiro Hamano

    PLoS Neglected Tropical Diseases   11 ( 9 )   e0005872   2017.9

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  • Spatial distribution and risk factors of Schistosoma haematobium and hookworm infections among schoolchildren in Kwale, Kenya Reviewed

    Evans Asena Chadeka, Sachiyo Nagi, Toshihiko Sunahara, Ngetich Benard Cheruiyot, Felix Bahati, Yuriko Ozeki, Manabu Inoue, Mayuko Osada-Oka, Mayuko Okabe, Yukio Hirayama, Mwatasa Changoma, Keishi Adach, Faith Mwende, Mihoko Kikuchi, Risa Nakamura, Yombo Dan Justin Kalenda, Satoshi Kaneko, Kenji Hirayama, Masaaki Shimada, Yoshio Ichinose, Sammy M. Njenga, Sohkichi Matsumoto, Shinjiro Hamano

    PLOS NEGLECTED TROPICAL DISEASES   11 ( 9 )   2017.9

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  • Mycobacterial DNA-binding protein 1 is critical for long term survival of Mycobacterium smegmatis and simultaneously coordinates cellular functions Reviewed

    Shymaa Enany, Yutaka Yoshida, Yoshitaka Tateishi, Yuriko Ozeki, Akihito Nishiyama, Anna Savitskaya, Takehiro Yamaguchi, Yukiko Ohara, Tadashi Yamamoto, Manabu Ato, Sohkichi Matsumoto

    SCIENTIFIC REPORTS   7 ( 1 )   6810   2017.7

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  • Effects of nutritional and ambient oxygen condition on biofilm formation in Mycobacterium avium subsp hominissuis via altered glycolipid expression Reviewed

    Takahiro Totani, Yukiko Nishiuchi, Yoshitaka Tateishi, Yutaka Yoshida, Hiromi Kitanaka, Mamiko Niki, Yukihiro Kaneko, Sohkichi Matsumoto

    SCIENTIFIC REPORTS   7   41775   2017.2

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  • p38α Activates Purine Metabolism to Initiate Hematopoietic Stem/Progenitor Cell Cycling in Response to Stress. Reviewed International journal

    Daiki Karigane, Hiroshi Kobayashi, Takayuki Morikawa, Yukako Ootomo, Mashito Sakai, Go Nagamatsu, Yoshiaki Kubota, Nobuhito Goda, Michihiro Matsumoto, Emi K Nishimura, Tomoyoshi Soga, Kinya Otsu, Makoto Suematsu, Shinichiro Okamoto, Toshio Suda, Keiyo Takubo

    Cell stem cell   19 ( 2 )   192 - 204   2016.8

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  • Meningococcal carriage rates in healthy individuals in Japan determined using Loop-Mediated Isothermal Amplification and oral throat wash specimens Reviewed

    Hideyuki Takahashi, Masae Haga, Tomimasa Sunagawa, Takehito Saitoh, Takeru Kitahara, Sohkichi Matsumoto, Makoto Ohnishi

    JOURNAL OF INFECTION AND CHEMOTHERAPY   22 ( 7-8 )   501 - 504   2016.7

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  • A New Screen for Tuberculosis Drug Candidates Utilizing a Luciferase-Expressing Recombinant Mycobacterium bovis Bacillus Calmette-Gueren Reviewed

    Yuriko Ozeki, Masayuki Igarashi, Matsumi Doe, Aki Tamaru, Naoko Kinoshita, Yoshitoshi Ogura, Tomotada Iwamoto, Ryuichi Sawa, Maya Umekita, Shymaa Enany, Yukiko Nishiuchi, Mayuko Osada-Oka, Tetsuya Hayashi, Mamiko Niki, Yoshitaka Tateishi, Masaki Hatano, Sohkichi Matsumoto

    PLOS ONE   10 ( 11 )   e0141658   2015.11

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  • Class-specific regulation of pro-inflammatory genes by MyD88 pathways and IκBζ. Reviewed

    Kayama H, Ramirez-Carrozzi VR, Yamamoto M, Mizutani T, Kuwata H, Iba H, Matsumoto M, Honda K, Smale ST, Takeda K

    The Journal of biological chemistry   290 ( 37 )   22446   2015.9

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  • Class-specific regulation of pro-inflammatory genes by MyD88 pathways and IκBζ. Reviewed

    Kayama H, Ramirez-Carrozzi VR, Yamamoto M, Mizutani T, Kuwata H, Iba H, Matsumoto M, Honda K, Smale ST, Takeda K

    The Journal of biological chemistry   290 ( 8 )   4815   2015.2

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  • Evaluation of Humoral Immunity to Mycobacterium tuberculosis-Specific Antigens for Correlation with Clinical Status and Effective Vaccine Development Reviewed

    Mamiko Niki, Maho Suzukawa, Shunsuke Akashi, Hideaki Nagai, Ken Ohta, Manabu Inoue, Makoto Niki, Yukihiro Kaneko, Kozo Morimoto, Atsuyuki Kurashima, Seigo Kitada, Sohkichi Matsumoto, Koichi Suzuki, Yoshihiko Hoshino

    JOURNAL OF IMMUNOLOGY RESEARCH   2015   527395   2015

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  • Whole-Genome Sequence of Mycobacterium kyorinense. Reviewed International journal

    Kouki Ohtsuka, Hiroaki Ohnishi, Eriko Nozaki, Jesus Pais Ramos, Enrico Tortoli, Shota Yonetani, Satsuki Matsushima, Yoshitaka Tateishi, Sohkichi Matsumoto, Takashi Watanabe

    Genome announcements   2 ( 5 )   2014.10

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    We report here the first draft genome sequence of Mycobacterium kyorinense, which was described in 2009 and exhibits significant pathogenicity to humans.

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  • Photodynamic Therapy Using Systemic Administration of 5-Aminolevulinic Acid and a 410-nm Wavelength Light-Emitting Diode for Methicillin-Resistant Staphylococcus aureus-Infected Ulcers in Mice Reviewed

    Kuniyuki Morimoto, Toshiyuki Ozawa, Kunio Awazu, Nobuhisa Ito, Norihiro Honda, Sohkichi Matsumoto, Daisuke Tsuruta

    PLOS ONE   9 ( 8 )   e105173   2014.8

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  • Serological Surveillance Development for Tropical Infectious Diseases Using Simultaneous Microsphere-Based Multiplex Assays and Finite Mixture Models Reviewed

    Fujii Yoshito, Kaneko Satoshi, Nzou Samson Muuo, Mwau Matilu, Njenga Sammy M, Tanigawa Chihiro, Kimotho James, Mwangi Anne Wanjiru, Kiche Ibrahim, Matsumoto Sohkichi, Niki Mamiko, Osada-Oka Mayuko, Ichinose Yoshio, Inoue Manabu, Itoh Makoto, Tachibana Hiroshi, Ishii Kazunari, Tsuboi Takafumi, Yoshida Lay Myint, Mondal Dinesh, Haque Rashidul, Hamano Shinjiro, Changoma Mwatasa, Hoshi Tomonori, Kamo Ken-ichi, Karama Mohamed, Miura Masashi, Hirayama Kenji

    PLOS NEGLECTED TROPICAL DISEASES   8 ( 7 )   2014.7

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  • Risk Factors and Spatial Distribution of Schistosoma mansoni Infection among Primary School Children in Mbita District, Western Kenya Reviewed

    Sachiyo Nagi, Evans A. Chadeka, Toshihiko Sunahara, Faith Mutungi, Yombo K. Dan Justin, Satoshi Kaneko, Yoshio Ichinose, Sohkichi Matsumoto, Sammy M. Njenga, Masahiro Hashizume, Masaaki Shimada, Shinjiro Hamano

    PLOS NEGLECTED TROPICAL DISEASES   8 ( 7 )   2014.7

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  • Risk Factors and Spatial Distribution of Schistosoma mansoni Infection among Primary School Children in Mbita District, Western Kenya Reviewed

    Sachiyo Nagi, Evans A. Chadeka, Toshihiko Sunahara, Faith Mutungi, Yombo K. Dan Justin, Satoshi Kaneko, Yoshio Ichinose, Sohkichi Matsumoto, Sammy M. Njenga, Masahiro Hashizume, Masaaki Shimada, Shinjiro Hamano

    PLoS Neglected Tropical Diseases   8 ( 7 )   e2991   2014

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  • Serological surveillance development for tropical infectious diseases using simultaneous microsphere-based multiplex assays and finite mixture models. Reviewed International journal

    Yoshito Fujii, Satoshi Kaneko, Samson Muuo Nzou, Matilu Mwau, Sammy M Njenga, Chihiro Tanigawa, James Kimotho, Anne Wanjiru Mwangi, Ibrahim Kiche, Sohkichi Matsumoto, Mamiko Niki, Mayuko Osada-Oka, Yoshio Ichinose, Manabu Inoue, Makoto Itoh, Hiroshi Tachibana, Kazunari Ishii, Takafumi Tsuboi, Lay Myint Yoshida, Dinesh Mondal, Rashidul Haque, Shinjiro Hamano, Mwatasa Changoma, Tomonori Hoshi, Ken-Ichi Kamo, Mohamed Karama, Masashi Miura, Kenji Hirayama

    PLoS neglected tropical diseases   8 ( 7 )   e3040   2014

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    BACKGROUND: A strategy to combat infectious diseases, including neglected tropical diseases (NTDs), will depend on the development of reliable epidemiological surveillance methods. To establish a simple and practical seroprevalence detection system, we developed a microsphere-based multiplex immunoassay system and evaluated utility using samples obtained in Kenya. METHODS: We developed a microsphere-based immuno-assay system to simultaneously measure the individual levels of plasma antibody (IgG) against 8 antigens derived from 6 pathogens: Entamoeba histolytica (C-IgL), Leishmania donovani (KRP42), Toxoplasma gondii (SAG1), Wuchereria bancrofti (SXP1), HIV (gag, gp120 and gp41), and Vibrio cholerae (cholera toxin). The assay system was validated using appropriate control samples. The assay system was applied for 3411 blood samples collected from the general population randomly selected from two health and demographic surveillance system (HDSS) cohorts in the coastal and western regions of Kenya. The immunoassay values distribution for each antigen was mathematically defined by a finite mixture model, and cut-off values were optimized. FINDINGS: Sensitivities and specificities for each antigen ranged between 71 and 100%. Seroprevalences for each pathogen from the Kwale and Mbita HDSS sites (respectively) were as follows: HIV, 3.0% and 20.1%; L. donovani, 12.6% and 17.3%; E. histolytica, 12.8% and 16.6%; and T. gondii, 30.9% and 28.2%. Seroprevalences of W. bancrofti and V. cholerae showed relatively high figures, especially among children. The results might be affected by immunological cross reactions between W. bancrofti-SXP1 and other parasitic infections; and cholera toxin and the enterotoxigenic E. coli (ETEC), respectively. INTERPRETATION: A microsphere-based multi-serological assay system can provide an opportunity to comprehensively grasp epidemiological features for NTDs. By adding pathogens and antigens of interest, optimized made-to-order high-quality programs can be established to utilize limited resources to effectively control NTDs in Africa.

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  • Direct detection of Mycobacterium avium in environmental water and scale samples by loop-mediated isothermal amplification

    Yukiko Nishiuchi, Aki Tamaru, Yasuhiko Suzuki, Seigo Kitada, Ryoji Maekura, Yoshitaka Tateishi, Mamiko Niki, Hisashi Ogura, Sohkichi Matsumoto

    JOURNAL OF WATER AND HEALTH   12 ( 2 )   211 - 219   2014

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  • [Molecular mechanisms of dormancy and drug tolerance in mycobacteria]. Reviewed

    Matsumoto S

    Nihon Hansenbyo Gakkai zasshi = Japanese journal of leprosy : official organ of the Japanese Leprosy Association   82 ( 3 )   119 - 22   2013.12

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  • T cell and B cell immunological responses by tuberculous antigens in Japanese populations with different bacterial antigen expressions Reviewed

    Sakakibara Yumi, Niki Mamiko, Sakagami Takuro, Ariga Haruyuki, Matsumoto Sohkichi, Inase Naohiko, Nagai Hideaki, Reche Pedro A, Hoshino Yoshihiko

    EUROPEAN RESPIRATORY JOURNAL   42   2013.9

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  • Reactivation of immune responses against Mycobacterium tuberculosis by boosting with the CpG oligomer in aged mice primarily vaccinated with Mycobacterium bovis BCG

    Keiichi Taniguchi, Takemasa Takii, Saburo Yamamoto, Jun-ichi Maeyama, Sumiko Iho, Mitsuo Maruyama, Narushi Iizuka, Yuriko Ozeki, Sohkichi Matsumoto, Tomohiro Hasegawa, Yuuji Miyatake, Saotomo Itoh, Kikuo Onozaki

    IMMUNITY & AGEING   10 ( 1 )   25 - 25   2013.6

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  • Critical Roles for Lipomannan and Lipoarabinomannan in Cell Wall Integrity of Mycobacteria and Pathogenesis of Tuberculosis

    Takeshi Fukuda, Takayuki Matsumura, Manabu Ato, Maho Hamasaki, Yukiko Nishiuchi, Yoshiko Murakami, Yusuke Maeda, Tamotsu Yoshimori, Sohkichi Matsumoto, Kazuo Kobayashi, Taroh Kinoshita, Yasu S. Morita

    MBIO   4 ( 1 )   e00472 - e00412   2013.1

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  • Antigen 85A and mycobacterial DNA-binding protein 1 are targets of immunoglobulin G in individuals with past tuberculosis.

    Osada-Oka Mayuko, Tateishi Yoshitaka, Hirayama Yukio, Ozeki Yuriko, Niki Mamiko, Kitada Seigo, Maekura Ryoji, Tsujimura Kunio, Koide Yukio, Ohara Naoya, Yamamoto Taro, Kobayashi Kazuo, Matsumoto Sohkichi

    Microbiol Immunol   57 ( 1 )   30 - 37   2013.1

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    Development of accurate methods for predicting progression of tuberculosis (TB) from the latent state is recognized as vitally important in controlling TB, because a majority of cases develop from latent infections. Past TB that has never been treated has a higher risk of progressing than does latent Mycobacterium tuberculosis infection in patients who have previously received treatment. Antibody responses against 23 kinds of M. tuberculosis proteins in individuals with past TB who had not been medicated were evaluated. These individuals had significantly higher concentrations of antibodies against Antigen 85A and mycobacterial DNA-binding protein 1 (MDP1) than did those with active TB and uninfected controls. In addition, immunohistochemistry revealed colocalization of tubercle bacilli, antigen 85 and MDP1 inside tuberculous granuloma lesions in an asymptomatic subject, showing that M. tuberculosis in lesions expresses both antigen 85 and MDP1. Our study suggests the potential usefulness of measuring antibody responses to antigen 85A and MDP1 for assessing the risk of TB progression.

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  • Antigen 85A and mycobacterial DNA-binding protein 1 are targets of immunoglobulin G in individuals with past tuberculosis. Reviewed

    Osada-Oka M, Tateishi Y, Hirayama Y, Ozeki Y, Niki M, Kitada S, Maekura R, Tsujimura K, Koide Y, Ohara N, Yamamoto T, Kobayashi K, Matsumoto S

    Microbiology and immunology   57 ( 1 )   30 - 37   2013.1

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  • Multicolor flow cytometric analyses of CD4+ T cell responses to Mycobacterium tuberculosis-related latent antigens

    Yoshiro Yamashita, Yoshihiko Hoshino, Mayuko Oka, Sokichi Matsumoto, Haruyuki Ariga, Hideaki Nagai, Masahiko Makino, Koya Ariyoshi, Yasuko Tsunetsugu-Yokota

    Japanese Journal of Infectious Diseases   66 ( 3 )   207 - 215   2013

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  • Whole-genome sequence of the potentially hypertransmissible multidrug-resistant Mycobacterium tuberculosis Beijing strain OM-V02_005

    Yoshitaka Tateishi, Aki Tamaru, Yoshitoshi Ogura, Mamiko Niki, Takayuki Wada, Taro Yamamoto, Kazuto Hirata, Tetsuya Hayashi, Sohkichi Matsumoto

    Genome Announcements   1 ( 4 )   2013

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    DOI： 10.1128/genomeA.00608-13

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  • Multicolor flow cytometric analyses of CD4+ T cell responses to Mycobacterium tuberculosis-related latent antigens. Reviewed

    Yamashita Y, Hoshino Y, Oka M, Matsumoto S, Ariga H, Nagai H, Makino M, Ariyoshi K, Tsunetsugu-Yokota Y

    Japanese journal of infectious diseases   66 ( 3 )   207 - 215   2013

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  • Glucose metabolism in macrophage suppresses intracellular growth of Mycobacterium tuberculosis Reviewed

    Oka Mayuko, Matsumoto Sohkichi, Kobayashi Kazuo, Nishiyama Masaki, Shiota Masayuki, Izumi Yasukatsu, Miura Katsuyuki, Iwao Hitoshi, Minamiyama Yukiko

    JOURNAL OF PHARMACOLOGICAL SCIENCES   121   124P - 124P   2013

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  • Protection by a recombinant Mycobacterium bovis Bacillus Calmette-Guérin vaccine expressing Shiga toxin 2 B subunit against Shiga toxin-producing Escherichia coli in mice

    Jun Fujii, Mariko Naito, Takashi Yutsudo, Sohkichi Matsumoto, Daniel P. Heatherly, Takeshi Yamada, Hideyuki Kobayashi, Shin-Ichi Yoshida, Tom Obrig

    Clinical and Vaccine Immunology   19 ( 12 )   1932 - 1937   2012.12

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  • Protection by a recombinant Mycobacterium bovis Bacillus Calmette-Guerin vaccine expressing Shiga toxin 2 B subunit against Shiga toxin-producing Escherichia coli in mice. Reviewed

    Fujii J, Naito M, Yutsudo T, Matsumoto S, Heatherly DP, Yamada T, Kobayashi H, Yoshida S, Obrig T

    Clinical and vaccine immunology : CVI   19 ( 12 )   1932 - 1937   2012.12

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  • Whole-genome sequence of the hypervirulent clinical strain Mycobacterium intracellulare M.i.198. International journal

    Yoshitaka Tateishi, Seigo Kitada, Keisuke Miki, Ryoji Maekura, Yoshitoshi Ogura, Yuriko Ozeki, Yukiko Nishiuchi, Mamiko Niki, Tetsuya Hayashi, Kazuto Hirata, Kazuo Kobayashi, Sohkichi Matsumoto

    Journal of bacteriology   194 ( 22 )   6336 - 6336   2012.11

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    We report herein the draft genome sequence of Mycobacterium intracellulare clinical strain M.i.198, which consistently exhibits hypervirulence in human patients, human macrophages in vitro, and immunocompetent mice.

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  • Whole-genome sequence of the hypervirulent clinical strain Mycobacterium intracellulare M.i.198. Reviewed

    Tateishi Y, Kitada S, Miki K, Maekura R, Ogura Y, Ozeki Y, Nishiuchi Y, Niki M, Hayashi T, Hirata K, Kobayashi K, Matsumoto S

    Journal of bacteriology   194 ( 22 )   6336   2012.11

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  • A novel mechanism of growth phase-dependent tolerance to isoniazid in mycobacteria

    Makoto Niki, Mamiko Niki, Yoshitaka Tateishi, Yuriko Ozeki, Teruo Kirikae, Astrid Lewin, Yusuke Inoue, Makoto Matsumoto, John L. Dahl, Hisashi Ogura, Kazuo Kobayashi, Sohkichi Matsumoto

    Journal of Biological Chemistry   287 ( 33 )   27743 - 27752   2012.8

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  • Dominant Incidence of Multidrug and Extensively Drug-Resistant Specific Mycobacterium tuberculosis Clones in Osaka Prefecture, Japan

    Aki Tamaru, Chie Nakajima, Takayuki Wada, Yajun Wang, Manabu Inoue, Ryuji Kawahara, Ryoji Maekura, Yuriko Ozeki, Hisashi Ogura, Kazuo Kobayashi, Yasuhiko Suzuki, Sohkichi Matsumoto

    PLOS ONE   7 ( 8 )   e42505 - e42505   2012.8

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  • A novel mechanism of growth phase-dependent tolerance to isoniazid in mycobacteria. Reviewed

    Niki M, Niki M, Tateishi Y, Ozeki Y, Kirikae T, Lewin A, Inoue Y, Matsumoto M, Dahl JL, Ogura H, Kobayashi K, Matsumoto S

    The Journal of biological chemistry   287 ( 33 )   27743 - 27752   2012.8

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  • Analysis of molecular mechanisms of the virulence and growth coordination of Mycobacterium tuberculosis

    MATSUMOTO Sohkichi

    Zeitschrift der Japanischen Mikrobiologische Gesellschaft   66 ( 4 )   531 - 537   2011.12

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  • Loss of anti-mycobacterial efficacy in mice over time following vaccination with Mycobacterium bovis bacillus Calmette-Guérin

    Yuriko Ozeki, Yukio Hirayama, Takemasa Takii, Saburo Yamamoto, Kazuo Kobayashi, Sohkichi Matsumoto

    Vaccine   29 ( 40 )   6881 - 6887   2011.9

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  • Loss of anti-mycobacterial efficacy in mice over time following vaccination with Mycobacterium bovis bacillus Calmette-Guerin Reviewed

    Yuriko Ozeki, Yukio Hirayama, Takemasa Takii, Saburo Yamamoto, Kazuo Kobayashi, Sohkichi Matsumoto

    VACCINE   29 ( 40 )   6881 - 6887   2011.9

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  • Mitochondrial density contributes to the immune response of macrophages to lipopolysaccharide via the MAPK pathway

    Emiko Kasahara, Atsuo Sekiyama, Mika Hori, Kenjiro Hara, Nozomi Takahashi, Masami Konishi, Eisuke F Sato, Sohkichi Matsumoto, Haruki Okamura, Masayasu Inoue

    FEBS Letters   585 ( 14 )   2263 - 2268   2011.7

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  • A Histone-Like Protein of Mycobacteria Possesses Ferritin Superfamily Protein-Like Activity and Protects against DNA Damage by Fenton Reaction

    Masaki Takatsuka, Mayuko Osada-Oka, Eisuke F. Satoh, Kengo Kitadokoro, Yukiko Nishiuchi, Mamiko Niki, Masayasu Inoue, Kazuhiro Iwai, Tetsuo Arakawa, Yoshihiro Shimoji, Hisashi Ogura, Kazuo Kobayashi, Anura Rambukkana, Sohkichi Matsumoto

    PLOS ONE   6 ( 6 )   e20985 - e20985   2011.6

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  • Development of avian influenza virus H5 DNA vaccine and MDP-1 gene of Mycobacterium bovis as genetic adjuvant

    Babak Jalilian, Abdul R. Omar, Mohd H. Bejo, Noorjahan B. Alitheen, Mehdi Rasoli, Sohkichi Matsumoto

    Genetic Vaccines and Therapy   8   4 - 4   2010.5

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    DOI： 10.1186/1479-0556-8-4

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  • Controlled expression of branch-forming mannosyltransferase is critical for mycobacterial lipoarabinomannan biosynthesis

    Chubert B. C. Sena, Takeshi Fukuda, Kana Miyanagi, Sohkichi Matsumoto, Kazuo Kobayashi, Yoshiko Murakami, Yusuke Maeda, Taroh Kinoshita, Yasu S. Morita

    Journal of Biological Chemistry   285 ( 18 )   13326 - 13336   2010.4

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  • Differential recruitment of CD63 and Rab7-interacting-lysosomal-protein to phagosomes containing Mycobacterium tuberculosis in macrophages

    Shintaro Seto, Sohkichi Matsumoto, Kunio Tsujimura, Yukio Koide

    MICROBIOLOGY AND IMMUNOLOGY   54 ( 3 )   170 - 174   2010.3

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    DOI： 10.1111/j.1348-0421.2010.00199.x

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  • Transient role of CD4+CD25+ regulatory T cells in mycobacterial infection in mice. Reviewed

    Ozeki Y, Sugawara I, Udagawa T, Aoki T, Osada-Oka M, Tateishi Y, Hisaeda H, Nishiuchi Y, Harada N, Kobayashi K, Matsumoto S

    International immunology   22 ( 3 )   179 - 189   2010.3

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  • Characterization of murine T-cell epitopes on mycobacterial DNA-binding protein 1 (MDP1) using DNA vaccination. International journal

    Suzuki Daisuke, Nagata Toshi, Eweda Ghada, Matsumoto Sohkichi, Matsumoto Makoto, Tsujimura Kunio, Koide Yukio

    Vaccine   28 ( 8 )   2020 - 2025   2010.2

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    Mycobacterial DNA-binding protein 1 (MDP1) is a major protein antigen in mycobacteria and induces protective immunity against Mycobacterium tuberculosis infection in mice. In this study we determined murine T-cell epitopes on MDP1 with MDP1 DNA immunization in mice. We analyzed interferon-gamma production from the MDP1 DNA-immune splenocytes in response to 20-mer overlapping peptides covering MDP1 protein. We identified several CD4+ T-cell epitopes in three inbred mouse strains and one CD8+ T-cell epitope in C57BL/6 mice. These T-cell epitopes would be feasible for analysis of the role of MDP1-specific T-cells in protective immunity and for future vaccine design against M. tuberculosis infection.

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  • Transient role of CD4+CD25+ regulatory T cells in mycobacterial infection in mice

    Yuriko Ozeki, Isamu Sugawara, Tadashi Udagawa, Toshiaki Aoki, Mayuko Osada-Oka, Yoshitaka Tateishi, Hajime Hisaeda, Yuji Nishiuchi, Nobuyuki Harada, Kazuo Kobayashi, Sohkichi Matsumoto

    International Immunology   22 ( 3 )   179 - 189   2010.2

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  • Mycobacteria exploit host hyaluronan for efficient extracellular replication

    Yukio Hirayama, Mamiko Yoshimura, Yuriko Ozeki, Isamu Sugawara, Tadashi Udagawa, Satoru Mizuno, Naoki Itano, Koji Kimata, Aki Tamaru, Hisashi Ogura, Kazuo Kobayashi, Sohkichi Matsumoto

    PLoS Pathogens   5 ( 10 )   e1000643 - e1000643   2009.10

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    DOI： 10.1371/journal.ppat.1000643

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  • Mycobacteria Exploit Host Hyaluronan for Efficient Extracellular Replication Reviewed

    Yukio Hirayama, Mamiko Yoshimura, Yuriko Ozeki, Isamu Sugawara, Tadashi Udagawa, Satoru Mizuno, Naoki Itano, Koji Kimata, Aki Tamaru, Hisashi Ogura, Kazuo Kobayashi, Sohkichi Matsumoto

    PLOS PATHOGENS   5 ( 10 )   e1000643   2009.10

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  • Dissection of Rab7 localization on Mycobacterium tuberculosis phagosome

    Shintaro Seto, Sohkichi Matsumoto, Isamu Ohta, Kunio Tsujimura, Yukio Koide

    Biochemical and Biophysical Research Communications   387 ( 2 )   272 - 277   2009.9

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  • High transmissibility of the modern Beijing Mycobacterium tuberculosis in homeless patients of Japan.

    Wada Takayuki, Fujihara Sami, Shimouchi Akira, Harada Makoto, Ogura Hisashi, Matsumoto Sohkichi, Hase Atsushi

    Tuberculosis (Edinb)   89 ( 4 )   252 - 255   2009.7

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    A population-based study of Mycobacterium tuberculosis isolated from homeless tuberculosis patients was performed during 2002-2004 in Osaka City, Japan. The data show that the ancient Beijing subfamily was predominant, whereas clustered isolates based on refined variable number of tandem repeats genotyping (19 loci) mainly belonged to the modern Beijing subfamily, suggesting its increased transmissibility.

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  • High transmissibility of the modern Beijing Mycobacterium tuberculosis in homeless patients of Japan Reviewed

    Takayuki Wada, Sami Fujihara, Akira Shimouchi, Makoto Harada, Hisashi Ogura, Sohkichi Matsumoto, Atsushi Hase

    TUBERCULOSIS   89 ( 4 )   252 - 255   2009.7

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  • Mycobacterium kyorinense sp nov., a novel, slow-growing species, related to Mycobacterium celatum, isolated from human clinical specimens

    Mitsuhiro Okazaki, Kiyofumi Ohkusu, Hiroyuki Hata, Hiroaki Ohnishi, Keiko Sugahara, Chizuko Kawamura, Nagatoshi Fujiwara, Sohkichi Matsumoto, Yukiko Nishiuchi, Kouichi Toyoda, Hajime Saito, Shota Yonetani, Yoko Fukugawa, Masayuki Yamamoto, Hiroo Wada, Akiko Sejimo, Akio Ebina, Hajime Goto, Takayuki Ezaki, Takashi Watanabe

    INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY   59 ( Pt 6 )   1336 - 1341   2009.6

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    DOI： 10.1099/ijs.0.000760-0

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  • Mycobacterium avium Complex Organisms Predominantly Colonize in the Bathtub Inlets of Patients' Bathrooms Reviewed

    Yukiko Nishiuchi, Aki Tamaru, Seigo Kitada, Takahiro Taguri, Sohkichi Matsumoto, Yoshitaka Tateishi, Mamiko Yoshimura, Yuriko Ozeki, Narumi Matsumura, Hisashi Ogura, Ryoji Maekura

    JAPANESE JOURNAL OF INFECTIOUS DISEASES   62 ( 3 )   182 - 186   2009.5

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  • Mycobacterium avium Complex Organisms Predominantly Colonize in the Bathtub Inlets of Patients' Bathrooms

    Yukiko Nishiuchi, Aki Tamaru, Seigo Kitada, Takahiro Taguri, Sohkichi Matsumoto, Yoshitaka Tateishi, Mamiko Yoshimura, Yuriko Ozeki, Narumi Matsumura, Hisashi Ogura, Ryoji Maekura

    JAPANESE JOURNAL OF INFECTIOUS DISEASES   62 ( 3 )   182 - 186   2009.5

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  • Virulence of Mycobacterium avium complex strains isolated from immunocompetent patients. Reviewed

    Tateishi Y, Hirayama Y, Ozeki Y, Nishiuchi Y, Yoshimura M, Kang J, Shibata A, Hirata K, Kitada S, Maekura R, Ogura H, Kobayashi K, Matsumoto S

    Microbial pathogenesis   46 ( 1 )   6 - 12   2009.1

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  • Lipocalin 2-Dependent Inhibition of Mycobacterial Growth in Alveolar Epithelium Reviewed

    Hiroyuki Saiga, Junichi Nishimura, Hirotaka Kuwata, Megumi Okuyama, Sohkichi Matsumoto, Shintaro Sato, Makoto Matsumoto, Shizuo Akira, Yasunobu Yoshikai, Kenya Honda, Masahiro Yamamoto, Kiyoshi Takeda

    JOURNAL OF IMMUNOLOGY   181 ( 12 )   8521 - 8527   2008.12

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  • Structural analysis and biosynthesis gene cluster of an antigenic glycopeptidolipid from Mycobacterium intracellulare. International journal

    Fujiwara Nagatoshi, Nakata Noboru, Naka Takashi, Yano Ikuya, Doe Matsumi, Chatterjee Delphi, McNeil Michael, Brennan Patrick J, Kobayashi Kazuo, Makino Masahiko, Matsumoto Sohkichi, Ogura Hisashi, Maeda Shinji

    J Bacteriol   190 ( 10 )   3613 - 3621   2008.5

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    Mycobacterium avium-Mycobacterium intracellulare complex (MAC) is the most common isolate of nontuberculous mycobacteria and causes pulmonary and extrapulmonary diseases. MAC species can be grouped into 31 serotypes by the epitopic oligosaccharide structure of the species-specific glycopeptidolipid (GPL) antigen. The GPL consists of a serotype-common fatty acyl peptide core with 3,4-di-O-methyl-rhamnose at the terminal alaninol and a 6-deoxy-talose at the allo-threonine and serotype-specific oligosaccharides extending from the 6-deoxy-talose. Although the complete structures of 15 serotype-specific GPLs have been defined, the serotype 16-specific GPL structure has not yet been elucidated. In this study, the chemical structure of the serotype 16 GPL derived from M. intracellulare was determined by using chromatography, mass spectrometry, and nuclear magnetic resonance analyses. The result indicates that the terminal carbohydrate epitope of the oligosaccharide is a novel N-acyl-dideoxy-hexose. By the combined linkage analysis, the oligosaccharide structure of serotype 16 GPL was determined to be 3-2&#039;-methyl-3&#039;-hydroxy-4&#039;-methoxy-pentanoyl-amido-3,6-dideoxy-beta-hexose-(1--&gt;3) -4

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  • Structural analysis and biosynthesis gene cluster of an antigenic glycopeptidolipid from Mycobacterium intracellulare. Reviewed International journal

    Fujiwara N, Nakata N, Naka T, Yano I, Doe M, Chatterjee D, McNeil M, Brennan PJ, Kobayashi K, Makino M, Matsumoto S, Ogura H, Maeda S

    Journal of bacteriology   190 ( 10 )   3613 - 3621   2008.5

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    Mycobacterium avium-Mycobacterium intracellulare complex (MAC) is the most common isolate of nontuberculous mycobacteria and causes pulmonary and extrapulmonary diseases. MAC species can be grouped into 31 serotypes by the epitopic oligosaccharide structure of the species-specific glycopeptidolipid (GPL) antigen. The GPL consists of a serotype-common fatty acyl peptide core with 3,4-di-O-methyl-rhamnose at the terminal alaninol and a 6-deoxy-talose at the allo-threonine and serotype-specific oligosaccharides extending from the 6-deoxy-talose. Although the complete structures of 15 serotype-specific GPLs have been defined, the serotype 16-specific GPL structure has not yet been elucidated. In this study, the chemical structure of the serotype 16 GPL derived from M. intracellulare was determined by using chromatography, mass spectrometry, and nuclear magnetic resonance analyses. The result indicates that the terminal carbohydrate epitope of the oligosaccharide is a novel N-acyl-dideoxy-hexose. By the combined linkage analysis, the oligosaccharide structure of serotype 16 GPL was determined to be 3-2'-methyl-3'-hydroxy-4'-methoxy-pentanoyl-amido-3,6-dideoxy-beta-hexose-(1-->3)-4-O-methyl-alpha-L-rhamnose-(1-->3)-alpha-L-rhamnose-(1-->3)-alpha-L-rhamnose-(1-->2)-6-deoxy-alpha-L-talose. Next, the 22.9-kb serotype 16-specific gene cluster involved in the glycosylation of oligosaccharide was isolated and sequenced. The cluster contained 17 open reading frames (ORFs). Based on the similarity of the deduced amino acid sequences, it was assumed that the ORF functions include encoding three glycosyltransferases, an acyltransferase, an aminotransferase, and a methyltransferase. An M. avium serotype 1 strain was transformed with cosmid clone no. 253 containing gtfB-drrC of M. intracellulare serotype 16, and the transformant produced serotype 16 GPL. Together, the ORFs of this serotype 16-specific gene cluster are responsible for the biosynthesis of serotype 16 GPL.

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  • Potent antimycobacterial activity of mouse secretory leukocyte protease inhibitor

    Junichi Nishimura, Hiroyuki Saiga, Shintaro Sato, Megumi Okuyama, Hisako Kayama, Hirotaka Kuwata, Sohkichi Matsumoto, Toshirou Nishida, Yoshiki Sawa, Shizuo Akira, Yasunobu Yoshikai, Masahiro Yamamoto, Kiyoshi Takeda

    JOURNAL OF IMMUNOLOGY   180 ( 6 )   4032 - 4039   2008.3

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  • Control of cell wall assembly by a histone-like protein in Mycobacteria.

    Katsube Tomoya, Matsumoto Sohkichi, Takatsuka Masaki, Okuyama Megumi, Ozeki Yuriko, Naito Mariko, Nishiuchi Yukiko, Fujiwara Nagatoshi, Yoshimura Mamiko, Tsuboi Takafumi, Torii Motomi, Oshitani Nobuhide, Arakawa Tetsuo, Kobayashi Kazuo

    J Bacteriol   189 ( 22 )   8241 - 8249   2007.11

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    Bacteria coordinate assembly of the cell wall as well as synthesis of cellular components depending on the growth state. The mycobacterial cell wall is dominated by mycolic acids covalently linked to sugars, such as trehalose and arabinose, and is critical for pathogenesis of mycobacteria. Transfer of mycolic acids to sugars is necessary for cell wall biogenesis and is mediated by mycolyltransferases, which have been previously identified as three antigen 85 (Ag85) complex proteins. However, the regulation mechanism which links cell wall biogenesis and the growth state has not been elucidated. Here we found that a histone-like protein has a dual concentration-dependent regulatory effect on mycolyltransferase functions of the Ag85 complex through direct binding to both the Ag85 complex and the substrate, trehalose-6-monomycolate, in the cell wall. A histone-like protein-deficient Mycobacterium smegmatis strain has an unusual crenellated cell wall structure and exhibits impaired cessation of glycolipid biosynthesis in the growth-retarded phase. Furthermore, we found that artificial alteration of the amount of the extracellular histone-like protein and the Ag85 complex changes the

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  • Control of cell wall assembly by a histone-like protein in Mycobacteria. Reviewed International journal

    Katsube T, Matsumoto S, Takatsuka M, Okuyama M, Ozeki Y, Naito M, Nishiuchi Y, Fujiwara N, Yoshimura M, Tsuboi T, Torii M, Oshitani N, Arakawa T, Kobayashi K

    Journal of bacteriology   189 ( 22 )   8241 - 8249   2007.11

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    Bacteria coordinate assembly of the cell wall as well as synthesis of cellular components depending on the growth state. The mycobacterial cell wall is dominated by mycolic acids covalently linked to sugars, such as trehalose and arabinose, and is critical for pathogenesis of mycobacteria. Transfer of mycolic acids to sugars is necessary for cell wall biogenesis and is mediated by mycolyltransferases, which have been previously identified as three antigen 85 (Ag85) complex proteins. However, the regulation mechanism which links cell wall biogenesis and the growth state has not been elucidated. Here we found that a histone-like protein has a dual concentration-dependent regulatory effect on mycolyltransferase functions of the Ag85 complex through direct binding to both the Ag85 complex and the substrate, trehalose-6-monomycolate, in the cell wall. A histone-like protein-deficient Mycobacterium smegmatis strain has an unusual crenellated cell wall structure and exhibits impaired cessation of glycolipid biosynthesis in the growth-retarded phase. Furthermore, we found that artificial alteration of the amount of the extracellular histone-like protein and the Ag85 complex changes the growth rate of mycobacteria, perhaps due to impaired down-regulation of glycolipid biosynthesis. Our results demonstrate novel regulation of cell wall assembly which has an impact on bacterial growth.

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  • Priming-boosting vaccination with recombinant Mycobacterium bovis bacillus Calmette-Guerin and a nonreplicating vaccinia virus recombinant leads to long-lasting and effective immunity

    Y Ami, Y Izumi, K Matsuo, K Someya, M Kanekiyo, S Horibata, N Yoshino, K Sakai, K Shinohara, S Matsumoto, T Yamada, S Yamazaki, N Yamamoto, M Honda

    JOURNAL OF VIROLOGY   79 ( 20 )   12871 - 12879   2005.10

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    DOI： 10.1128/JVI.79.20.12871-12879.2005

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  • DNA augments antigenicity of mycobacterial DNA-binding protein 1 and confers protection against Mycobacterium tuberculosis infection in mice

    S Matsumoto, M Matsumoto, K Umemori, Y Ozeki, M Furugen, T Tatsuo, Y Hirayama, S Yamamoto, T Yamada, K Kobayashi

    JOURNAL OF IMMUNOLOGY   175 ( 1 )   441 - 449   2005.7

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  • Mycobacterial trehalose 6,6 '-dimycolate preferentially induces type 1 helper T cell responses through signal transducer and activator of transcription 4 protein

    R Oiso, N Fujiwara, H Yamagami, S Maeda, S Matsumoto, S Nakamura, N Oshitani, T Matsumoto, T Arakawa, K Kobayashi

    MICROBIAL PATHOGENESIS   39 ( 1-2 )   35 - 43   2005.7

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    DOI： 10.1016/j.micpath.2005.03.003

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  • Mycobacterial codon optimization enhances antigen expression and virus-specific immune responses in recombinant Mycobactetium bovis bacille Calmette-Guerin expressing human immunodeficiency virus type 1 Gag

    M Kanekiyo, K Matsuo, M Hamatake, T Hamano, T Ohsu, S Matsumoto, T Yamada, S Yamazaki, A Hasegawa, N Yamamoto, M Honda

    JOURNAL OF VIROLOGY   79 ( 14 )   8716 - 8723   2005.7

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    DOI： 10.1128/JVI.79.14.8716-8723.2005

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  • Close correlation of streptococcal DNase B (sdaB) alleles with emm genotypes in Streptococcus pyogenes Reviewed

    M Matsumoto, K Sakae, S Hashikawa, K Torii, T Hasegawa, T Horii, M Endo, R Okuno, S Murayama, K Hirasawa, R Suzuki, J Isobe, D Tanaka, C Katsukawa, A Tamaru, M Tomita, K Ogata, T Ikebe, H Watanabe, M Ohta

    MICROBIOLOGY AND IMMUNOLOGY   49 ( 10 )   925 - 929   2005

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  • Extracellular mycobacterial DNA-binding protein 1 participates in mycobacterium-lung epithelial cell interaction through hyaluronic acid

    K Aoki, S Matsumoto, Y Hirayama, T Wada, Y Ozeki, M Niki, P Domenech, K Umemori, S Yamamoto, A Mineda, M Matsumoto, K Kobayashi

    JOURNAL OF BIOLOGICAL CHEMISTRY   279 ( 38 )   39798 - 39806   2004.9

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    DOI： 10.1074/jbc.M402677200

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  • Combined intrarectal/intradermal inoculation of recombinant Mycobacterium bovis bacillus Calmette-Guerin (BCG) induces enhanced immune responses against the inserted HIV-1V3 antigen Reviewed

    M Kawahara, K Matsuo, T Nakasone, T Hiroi, H Kiyono, S Matsumoto, T Yamada, N Yamamoto, M Honda

    VACCINE   21 ( 3-4 )   158 - 166   2002.12

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    DOI： 10.1016/S0264-410X(02)00465-6

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  • Interaction between the N-terminal and middle regions is essential for the in vivo function of HSP90 molecular chaperone Reviewed

    S Matsumoto, E Tanaka, TK Nemoto, T Ono, T Takagi, J Imai, Y Kimura, Yahara, I, T Kobayakawa, T Ayuse, K Oi, A Mizuno

    JOURNAL OF BIOLOGICAL CHEMISTRY   277 ( 38 )   34959 - 34966   2002.9

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    DOI： 10.1074/jbc.M203038200

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  • Discovery of immunostimulatory CpG-DNA and its application to tuberculosis vaccine development Reviewed

    S Yamamoto, T Yamamoto, Y Nojima, K Umemori, S Phalen, DN McMurray, E Kuramoto, S Iho, R Takauji, Y Sato, T Yamada, N Ohara, S Matsumoto, Y Goto, K Matsuo, T Tokunaga

    JAPANESE JOURNAL OF INFECTIOUS DISEASES   55 ( 2 )   37 - 44   2002.4

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  • Human intelectin is a novel soluble lectin that recognizes galactofuranose in carbohydrate chains of bacterial cell wall

    S Tsuji, J Uehori, M Matsumoto, Y Suzuki, A Matsuhisa, K Toyoshima, T Seya

    JOURNAL OF BIOLOGICAL CHEMISTRY   276 ( 26 )   23456 - 23463   2001.6

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  • Identification of the mycobacterial DNA-binding protein 1 region which suppresses transcription in vitro

    Makoto Furugen, Sohkichi Matsumoto, Takemitsu Matsuo, Makoto Matsumoto, Takeshi Yamada

    Microbial Pathogenesis   30 ( 3 )   129 - 138   2001

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    DOI： 10.1006/mpat.2000.0416

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  • A Toll-like receptor recognizes bacterial DNA. International journal

    H Hemmi, O Takeuchi, T Kawai, T Kaisho, S Sato, H Sanjo, M Matsumoto, K Hoshino, H Wagner, K Takeda, S Akira

    Nature   408 ( 6813 )   740 - 5   2000.12

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    DNA from bacteria has stimulatory effects on mammalian immune cells, which depend on the presence of unmethylated CpG dinucleotides in the bacterial DNA. In contrast, mammalian DNA has a low frequency of CpG dinucleotides, and these are mostly methylated; therefore, mammalian DNA does not have immuno-stimulatory activity. CpG DNA induces a strong T-helper-1-like inflammatory response. Accumulating evidence has revealed the therapeutic potential of CpG DNA as adjuvants for vaccination strategies for cancer, allergy and infectious diseases. Despite its promising clinical use, the molecular mechanism by which CpG DNA activates immune cells remains unclear. Here we show that cellular response to CpG DNA is mediated by a Toll-like receptor, TLR9. TLR9-deficient (TLR9-/-) mice did not show any response to CpG DNA, including proliferation of splenocytes, inflammatory cytokine production from macrophages and maturation of dendritic cells. TLR9-/- mice showed resistance to the lethal effect of CpG DNA without any elevation of serum pro-inflammatory cytokine levels. The in vivo CpG-DNA-mediated T-helper type-1 response was also abolished in TLR9-/- mice. Thus, vertebrate immune systems appear to have evolved a specific Toll-like receptor that distinguishes bacterial DNA from self-DNA.

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  • Mycobacterium bovis bacillus calmette-guerin induces protective immunity against infection by Plasmodium yoelii at blood-stage depending on shifting immunity toward Th1 type and inducing protective IgG2a after the parasite infection Reviewed

    S Matsumoto, H Yukitake, H Kanbara, H Yamada, A Kitamura, T Yamada

    VACCINE   19 ( 7-8 )   779 - 787   2000.11

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  • The gene encoding mycobacterial DNA-binding protein I (MDPI) transformed rapidly growing bacteria to slowly growing bacteria Reviewed

    S Matsumoto, M Furugen, H Yukitake, T Yamada

    FEMS MICROBIOLOGY LETTERS   182 ( 2 )   297 - 301   2000.1

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  • Long-lasting protective immunity against rodent malaria parasite infection at the blood stage by recombinant BCG secreting merozoite surface protein-1 Reviewed

    S Matsumoto, H Yukitake, H Kanbara, T Yamada

    VACCINE   18 ( 9-10 )   832 - 834   1999.12

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  • Antibody-independent classical complement pathway activation and homologous C3 deposition in xeroderma pigmentosum cell lines

    M Kurita, M Matsumoto, S Tsuji, M Kawakami, Y Suzuki, H Hayashi, K Toyoshima, T Seya

    CLINICAL AND EXPERIMENTAL IMMUNOLOGY   116 ( 3 )   547 - 553   1999.6

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  • Host immune responses to ribosome, ribosomal proteins, and RNA from Mycobacterium bovis bacille de Calmette-Gúerin. Reviewed

    Miyazaki C, Ohara N, Yukitake H, Kinomoto M, Matsushita K, Matsumoto S, Mizuno A, Yamada T

    Vaccine   17 ( 3 )   245 - 251   1999.1

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  • Post-translational modification and intracellular localization of a splice product of CD46 cloned from human testis: role of the intracellular domains in O-glycosylation

    T Hara, Y Suzuki, T Nakazawa, H Nishimura, S Nagasawa, M Nishiguchi, M Matsumoto, M Hatanaka, M Kitamura, T Seya

    IMMUNOLOGY   93 ( 4 )   546 - 555   1998.4

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    DOI： 10.1046/j.1365-2567.1998.00455.x

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  • Characterization of the transcriptional initiation regions of genes for the major secreted protein antigens 85C and MPB51 of Mycobacterium bovis BCG. Reviewed

    Ohara N, Nishiyama T, Ohara-Wada N, Matsumoto S, Matsuo T, Yamada T

    Microbial pathogenesis   23 ( 5 )   303 - 310   1997.11

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  • STAT3 activation is a critical step in gp130-mediated terminal differentiation and growth arrest of a myeloid cell line. Reviewed

    M. Minami, M. Inoue, S. Wei, K. Takeda, M. Matsumoto, T. Kishimoto, S. Akira

    Proceedings of the National Academy of Sciences   93 ( 9 )   3963 - 3966   1996.4

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  • High expression of membrane cofactor protein of complement (CD46) in human leukaemia cell lines: Implication of an alternatively spliced form containing the STA domain in CD46 up-regulation

    T Hara, Y Suzuki, T Semba, M Hatanaka, M Matsumoto, T Seya

    SCANDINAVIAN JOURNAL OF IMMUNOLOGY   42 ( 6 )   581 - 590   1995.12

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  • Leprosy and Vaccine

    MATSUMOTO Sohkichi, YAMADA Takeshi

    JAPANESE JOURNAL OF LEPROSY   64 ( 3 )   163 - 173   1995.11

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  • Study of a antigen from Mycobacterium intracellulare and use of PCR for the rapid identification of Mycobacterium intracellulare. Reviewed

    Kitaura H, Ohara N, Naito M, Nishiyama T, Wada N, Matsumoto S, Matsuo T, Hotokezaka H, Hayashida H, Kobayashi K, Yamada T

    Procceedings to 4th Western Pacific Congress on Chemotherapy and Infectious Diseases   10 ( 3 )   585 - 586   1994

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  • Structure and immunological properties of major secreted antigen a and related antigens of mycobacteria. Reviewed

    Ohara N, Kitaura H, Naito M, Nishiyama T, Wada N, Matsumoto S, Matsuo T, Hotokezaka H, Hayashida H, Yamada T

    Procceedings to 4th Western Pacifuc Congress on Chemotherapy and Infectious Diseases   10 ( 3 )   628 - 629   1994

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  • Regulation of MPB70 gene expression between two major BCG substrains. Reviewed

    Matsuo T, Ohara N, Matsumoto S, Kitaura H, Naito M, Wada N, Nishiyama T, Hotokezaka H, Hayashida H, Mizuno A, Yamada T

    Procceedings to 4th Western Pacifuc Congress on Chemotherapy and Infectious Diseases   10 ( 3 )   590 - 591   1994

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Books

  • 非結核性抗酸菌症診療Up to date

    森本, 耕三, 中川, 拓, 倉島, 篤行, 小川, 賢二（ Role： Joint author ,  M. intracellulare研究の最前線；何が分かってきたの。M. aviumとなにが違うの？）

    南江堂  2025.4  （ ISBN:9784524210442 ）

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    Total pages：xi, 363p   Language：Japanese

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  • 標準微生物学

    錫谷, 達夫, 松本, 哲哉（ Role： Joint author ,  抗酸菌）

    医学書院  2024.2  （ ISBN:9784260053440 ）

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    Total pages：xiv, 671p   Language：Japanese

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  • バイオフィルム革新的制御技術

    松本 壮吉、立石 善隆（ Role： Joint author ,  マイコバクテリウム属細菌（抗酸菌）による疾病とバイオフィルム形成）

    エヌ・ティー・エス  2023.6  （ ISBN:9784860438340 ）

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  • BCG : TB vaccine : application against tuberculosis and other diseases

    Yuriko Ozeki, Akihito Nishiyama, Mamiki Niki, Sohkichi Matsumoto（ Role： Joint author ,  Host and bacterial factors that regulate Mycobacterium tuberculosis infection and persistence）

    Japan Anti-Tuberculosis Association  2022.8  （ ISBN:9784874513224 ）

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  • 創薬研究者がこれだけは知っておきたい最新のウイルス学

    技術情報協会（ Role： Joint author ,  BCGのウイルス感染症に対する効果と組換えBCG）

    技術情報協会  2021.8  （ ISBN:9784861048555 ）

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    Total pages：602p   Language：Japanese

    CiNii Books

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  • Microbiology

    （ Role： Joint author ,  Mycobacteria）

    2021.3  （ ISBN:9784260043311 ）

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    Total pages：xiv, 690p   Language：Japanese

    CiNii Books

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  • シンプル微生物学

    松本 壮吉（ Role： Joint author ,  マイコバクテリウム属、アクチノマイセスとノカルジア）

    南江堂  2018 

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  • 結核

    松本 壮吉（ Role： Joint author ,  結核の潜在化と発症機構）

    医薬ジャーナル社  2017 

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  • 南山堂医学大事典

    松本 壮吉（ Role： Joint author ,  結核菌）

    南山堂  2015 

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  • 病原微生物学

    西山 晃史, 松本 壮吉（ Role： Joint author ,  抗酸菌と放線菌）

    東京化学同人  2014 

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  • 微生物の簡易迅速検査法

    仁木 誠, 松本 壮吉（ Role： Joint author ,  グラム陰性細菌）

    テクノシステム  2013 

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  • 人獣共通感染症

    西内 由紀子, 立石 善隆, 山田 毅, 松本 壮吉（ Role： Joint author ,  非結核性抗酸菌症）

    医薬ジャーナル社  2011 

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  • BCG vaccine and adjuvant

    NIKI Mamiko, MATSUMOTO Sohkichi（ Role： Joint author ,  Host and bacterial factors that regulate Mycobacterium tuberculosis infection and persistence）

    2011 

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  • 結核Up to Date

    松本 壮吉（ Role： Joint author ,  分子生物学から見た結核研究の現在）

    南江堂  2005 

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MISC

  • 野生型結核菌抗原を用いた抗体検出による活動性結核の診断と発症予測法の検討

    山崎 智也, 石川 智史, 田村 敏生, 塚本 裕美子, Nyoman Desak, 吉田 豊, 尾関 百合子, 西山 晃史, 立石 善隆, 松本 壮吉

    日本細菌学雑誌   78 ( 1 )   69 - 69   2023.2

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  • Identification of a new type of enzyme that reduces E- and Z-isoprene units

    阿部透, 若松のぞみ, 西山晃史, 立石善隆, 松本壮吉, 上田大次郎, 佐藤努

    日本農芸化学会大会講演要旨集(Web)   2023   2023

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  • Functional analysis of a new type of Z, E-mixed prenyl reductase from mycobacteria

    阿部透, 袴田真理子, 西山晃史, 立石善隆, 松本壮吉, 邊見久, 上田大次郎, 佐藤努

    日本農芸化学会大会講演要旨集(Web)   2022   2022

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  • E-及びZ-イソプレンユニットを還元する新しいタイプの酵素の同定

    阿部透, 若松のぞみ, 西山晃史, 立石善隆, 松本壮吉, 上田大次郎, 佐藤努

    イソプレノイド研究会例会講演要旨集   32nd   2022

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  • マイコバクテリア由来新規Z,E混成型プレニル基還元酵素の機能解析によるセスクアテルペン生合成の洞察

    阿部透, 袴田真理子, 西山晃史, 立石善隆, 松本壮吉, 邊見久, 上田大次郎, 佐藤努

    イソプレノイド研究会例会講演要旨集   31st (CD-ROM)   2021

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  • マイコバクテリア由来新規Z,E混成型プレニル基還元酵素の機能解析

    阿部透, 袴田真理子, 西山晃史, 立石善隆, 松本壮吉, 邊見久, 上田大次郎, 佐藤努

    日本放線菌学会大会講演要旨集   35th (CD-ROM)   2021

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  • GENOME ANALYSIS OF MYCOBACTERIUM TUBERCULOSIS BEIJING STRAINS ISOLATED FROM EARLY-ONSET AND LONG TERM LATENT POST-ONSET

    袴田真理子, 袴田真理子, 瀧原速仁, 岩本朋忠, 岩本朋忠, 田丸亜貴, 尾関百合子, 西山晃史, 立石善隆, 菊地利明, 奥田修二郎, 松本壮吉

    結核(Web)   96 ( 3 )   2021

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  • Genome analysis of Beijing lineage of Mtb and monitoring mycobacterial infection by CUBIC

    袴田真理子, 袴田真理子, 瀧原速仁, 尾関百合子, 西山晃史, 立石善隆, 大橋璃子, 奥田修二郎, 田井中一貴, 菊地利明, 松本壮吉

    日本細菌学雑誌(Web)   76 ( 1 )   2021

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  • 抗結核化合物OCT313と類縁化合物の休眠期結核菌に対する抗菌活性の検討

    瀧井猛将, 瀧井猛将, 安田直美, 長谷川倫宏, 黒石隆司, 堀田康弘, 堀田康弘, 伊藤佐生智, 前田伸司, 和田崇之, 松本壮吉, 肥田重明

    微生物シンポジウム講演要旨集   33rd   2021

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  • Existence of extracellular DNA in pathogenic mycobacteria and its role in mycobacterial physiology(和訳中)

    イリノフ・アレクサンドル, シャバン・アミナ, 袴田 真理子, 西山 晃史, 尾関 百合子, 福島 由華里, 中島 千絵, 立石 善隆, 鈴木 定彦, 松本 壮吉

    日本細菌学雑誌   75 ( 1 )   74 - 74   2020.1

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  • 抗酸菌症治療薬を目指した標的蛋白質の発現と精製

    大原 由貴子, 小林 悠, 尾関 百合子, 西山 晃史, 立石 善隆, 奥田 修二郎, 神谷 重樹, 北所 健悟, 松本 壮吉

    日本細菌学雑誌   75 ( 1 )   74 - 74   2020.1

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  • 早期発症者と長期潜伏後発症者より分離した結核菌北京株のゲノム変異解析

    袴田真理子, 袴田真理子, 瀧原速仁, 岩本朋忠, 田丸亜貴, 尾関百合子, 西山晃史, 菊地利明, 奥田修二郎, 松本壮吉

    結核(Web)   95 ( 5 )   2020

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  • Comparison of differential gene expression in mycobacterial biofilm formation vs dormancy

    西内由紀子, 大田篤, 矢野大和, 岩本朋忠, 阿戸学, 松本壮吉, 大原直也, 丸山史人

    Bacterial Adherence & Biofilm   33   2020

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  • Higher Genome Mutation Rates of a Beijing lineage of M. tuberculosis during LTBI

    袴田真理子, 袴田真理子, 瀧原速仁, 岩本朋忠, 田丸亜貴, 尾関百合子, 西山晃史, 立石善隆, 菊地利明, 奥田修二郎, 松本壮吉

    日本細菌学雑誌(Web)   75 ( 1 )   2020

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  • 【結核・非結核性抗酸菌症-エキスパートが教える 実臨床に役立つ最新知見】結核・非結核性抗酸菌症の基礎研究 結核免疫防御機能

    尾関 百合子, 松本 壮吉

    呼吸器ジャーナル   66 ( 4 )   643 - 649   2018.11

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    Other Link： http://search.jamas.or.jp/link/ui/2019048397

  • 病原性抗酸菌はヒト赤血球にin vitroで感染する

    西内 由紀子, 立石 善隆, 北田 清悟, 尾関 百合子, 前倉 亮治, 松本 壮吉

    結核   93 ( 4 )   285 - 285   2018.4

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  • 結核菌の増殖につながるマクロファージ由来因子のスクリーニング

    岡 真優子, 佐藤 睦, 小林 慧子, 南山 幸子, 尾関 百合子, 松本 壮吉

    日本栄養・食糧学会大会講演要旨集   72回   285 - 285   2018.4

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  • 結核菌の増殖につながるマクロファージ由来因子のスクリーニング

    岡 真優子, 佐藤 睦, 小林 慧子, 南山 幸子, 尾関 百合子, 松本 壮吉

    日本栄養・食糧学会大会講演要旨集   72回   285 - 285   2018.4

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  • 2016年、キュウリを原因とした腸管出血性大腸菌O157の集団感染

    尾鶴 亮, 立石 善隆, 小西 典子, 松本 壮吉, 松葉 隆司, 藤井 潤

    日本細菌学雑誌   73 ( 1 )   68 - 68   2018.2

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  • 誘導型発現制御系を用いた抗酸菌mycobacterial DNA-binding protein 1の機能解析(Conditional control of mycobacterial DNA-binding protein 1 expression in mycobacteria)

    Savitskaya Anna, 西山 晃史, 松本 壮吉

    日本細菌学雑誌   73 ( 1 )   97 - 97   2018.2

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  • 潜在期結核菌抗原の精製と感染診断への応用

    大原 由貴子, 尾関 百合子, 立石 善隆, 西山 晃史, 山本 三郎, 中川 一路, 松本 壮吉

    日本細菌学雑誌   73 ( 1 )   64 - 64   2018.2

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  • 病原性抗酸菌はヒト赤血球にin vitroで感染する(Pathogenic mycobacteria infect human erythrocytes in vitro)

    西内 由紀子, 立石 善隆, 尾関 百合子, 山口 雄大, 松本 壮吉

    日本細菌学雑誌   73 ( 1 )   41 - 41   2018.2

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  • カニクイザルを用いたMDP1とG9.1からなる結核ブースターワクチン候補の有効性評価

    前山 順一, 林 大介, 山本 十糸子, 向井 徹, 岡林 佐知, 田村 敏生, 山崎 利雄, 尾関 百合子, 松本 壮吉, 山本 三郎

    日本細菌学雑誌   73 ( 1 )   132 - 132   2018.2

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  • HDLはミコバクテリア感染ヒトマクロファージによる腫瘍壊死因子α産生を阻害する(HDL suppresses tumor necrosis factor alpha production by mycobacteria-infected human macrophages)

    尾関 百合子, 井上 学, 仁木 満美子, 岡 真優子, 松本 壮吉

    日本細菌学雑誌   73 ( 1 )   121 - 121   2018.2

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  • 2016年、キュウリを原因とした腸管出血性大腸菌O157の集団感染

    尾鶴 亮, 立石 善隆, 小西 典子, 松本 壮吉, 松葉 隆司, 藤井 潤

    日本細菌学雑誌   73 ( 1 )   68 - 68   2018.2

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  • 【生体および環境におけるバイオフィルム】 バイオフィルム感染症の診断・治療・予防 抗酸菌感染症

    松本 壮吉

    臨床と微生物   45 ( 1 )   063 - 067   2018.1

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  • Spatial distribution and risk factors of Schistosoma haematobium and hookworm infections among schoolchildren in Kwale, Kenya

    CHADEKA Evans Asena, NAGI Sachiyo, SUNAHARA Toshihiko, CHERUIYOT Ngetich Benard, BAHATI Felix, OZEKI Yuriko, INOUE Manabu, OSADA-OKA Mayuko, OKABE Mayuko, HIRAYAMA Yukio, CHANGOMA Mwatasa, ADACHI Keishi, MWENDE Faith, KIKUCHI Mihoko, NAKAMURA Risa, KALENDA Yombo Dan Justin, KANEKO Satoshi, KANEKO Satoshi, HIRAYAMA Kenji, SHIMADA Masaaki, SHIMADA Masaaki, ICHINOSE Yoshio, ICHINOSE Yoshio, NJENGA Sammy M., MATSUMOTO Sohkichi, HAMANO Shinjiro, HAMANO Shinjiro

    日本寄生虫学会大会プログラム・抄録集   87th   2018

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  • メチシリン耐性黄色ブドウ球菌に対するヤスダヨーグルトの抗菌活性の検討

    田島 陽介, 立石 善隆, 亀山 仁史, 松本 壮吉, 若井 俊文

    新潟医学会雑誌   131 ( 11 )   645 - 653   2017.11

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  • CONSIDERATION OF IMPROVEMENT MEASURES FROM LIMITATIONS OF IMMUNOLOGICAL TESTS―INCLUDING INTERFERON-γ RELEASE AND ANTIBODY-BASED DETECTION ASSAYS―FOR MYCOBACTERIUM TUBERCULOSIS INFECTION

    92 ( 9 )   551 - 558   2017.9

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  • 低栄養条件下における非結核性抗酸菌のバイオフィルム形成

    西内 由紀子, 戸谷 孝洋, 金子 幸弘, 松本 壮吉

    BACTERIAL ADHERENCE & BIOFILM   30   29 - 32   2017.5

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  • 潜在期結核菌抗原の精製と感染診断への応用(Significance of the histone-like protein with the native structure for diagnosis of asymptomatic tuberculosis)

    西田 由貴子, 尾関 百合子, 立石 善隆, 西山 晃史, 山本 三郎, 中川 一路, 松本 壮吉

    日本細菌学雑誌   72 ( 1 )   161 - 161   2017.2

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  • 潜在性結核感染症の診断と治療 抗酸菌の「長生き」のメカニズムと結核対策への応用

    松本 壮吉

    結核   92 ( 2 )   182 - 182   2017.2

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  • 抗酸菌における誘導発現系を用いたmycobacterial DNA-binding protein 1の機能解析(Conditional expression of mycobacterial DNA-binding protein 1 function in mycobacteria)

    Savitskaya Anna G, 西山 晃史, 大原 直也, 松本 壮吉

    日本細菌学雑誌   72 ( 1 )   97 - 97   2017.2

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  • 非結核性抗酸菌のバイオフィルム形成における栄養条件とGlycopeptidolipidの役割

    西内 由紀子, 戸谷 孝洋, 立石 善隆, 金子 幸弘, 松本 壮吉

    日本細菌学雑誌   72 ( 1 )   81 - 81   2017.2

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  • 咽頭うがい液を用いた髄膜炎菌の健康者保菌調査の実施

    高橋 英之, 羽賀 將衛, 砂川 富正, 齋藤 剛仁, 北原 武尊, 松本 壮吉, 大西 真

    日本細菌学雑誌   72 ( 1 )   73 - 73   2017.2

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  • 遅延型過敏反応から検討したMDP1およびG9.1からなる結核ブースターワクチン候補の免疫条件

    前山 順一, 山崎 利雄, 林 大介, 山本 十糸子, 尾関 百合子, 鈴木 史子, 山口 雄大, 松本 壮吉, 伊保 澄子, 山本 三郎, 網 康至, 須崎 百合子, 後藤 義孝

    日本細菌学雑誌   72 ( 1 )   61 - 61   2017.2

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  • 抗酸菌の長期の生存に必須な細胞機能のヒストン様タンパク質依存的な制御(Histone-like protein-dependent control of mycobacterial functions critical for long-term survival)

    西山 晃史, Enany Shymaa, 立石 善隆, 尾関 百合子, Savitskaya Anna G, 山口 雄大, 西田 由貴子, 阿戸 学, 松本 壮吉

    日本細菌学雑誌   72 ( 1 )   97 - 97   2017.2

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  • 結核・抗酸菌に特徴的な薬剤標的と新規薬剤の開発研究

    松本 壮吉

    感染症学雑誌   91 ( 1 )   41 - 42   2017.1

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  • 結核・抗酸菌に特徴的な薬剤標的と新規薬剤の開発研究

    松本 壮吉

    日本化学療法学会雑誌   65 ( 1 )   50 - 51   2017.1

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  • Mycobacterium kyorinenseおよび近縁種Mycobacterium celatumの薬剤耐性関連遺伝子の解析

    大西 宏明, 米谷 正太, 大塚 弘毅, 荒木 光二, 松本 壮吉, 立石 善隆, 河合 伸, 渡邊 卓

    感染症学雑誌   91 ( 1 )   100 - 100   2017.1

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  • 遅延型過敏反応から検討したMDP1およびG9.1からなる結核ブースターワクチン候補の免疫条件

    前山順一, 山崎利雄, 林大介, 林大介, 山本十糸子, 山本十糸子, 尾関百合子, 鈴木史子, 山口雄大, 松本壮吉, 伊保澄子, 山本三郎, 山本三郎

    日本細菌学雑誌(Web)   72 ( 1 )   61(J‐STAGE)   2017

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  • 新規結核菌抗原MDP1とCpG ODN G9.1アジュバントからなる結核ブースターワクチンのカニクイザルに対する有効性の検討

    山本三郎, 山本三郎, 林大介, 林大介, 山本十糸子, 山本十糸子, 小山明, 前山順一, 網康至, 須崎百合子, 向井徹, 岡林佐知, 田村敏生, 山崎利雄, 松本壮吉, 尾関百合子, 鈴木史子, 後藤義孝

    日本ワクチン学会学術集会プログラム・抄録集   21st   101   2017

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  • ケニア共和国成人を対象としたBCGブースターワクチン候補抗原の適性検討

    尾関百合子, 濱野真二郎, 松本壮吉, 岡真優子, 立石善隆

    長崎大学熱帯医学研究拠点共同研究報告集   2015   25‐29   2016.8

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    J-GLOBAL

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  • 低栄養条件下における非結核性抗酸菌のバイオフィルム形成

    西内 由紀子, 戸谷 孝洋, 金子 幸弘, 松本 壮吉

    日本バイオフィルム学会学術集会プログラム・抄録集   30回   37 - 37   2016.7

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  • バイオフィルム形成と環境中気体組成

    西内 由紀子, 戸谷 孝洋, 金子 幸弘, 松本 壮吉

    BACTERIAL ADHERENCE & BIOFILM   29   31 - 34   2016.5

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  • 非結核性抗酸菌のバイオフィルム形成における細胞壁糖脂質の役割

    西内 由紀子, 立石 善隆, 金子 幸弘, 松本 壮吉

    結核   91 ( 3 )   352 - 352   2016.3

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  • MDP1によるマイコバクテリア代謝抑制(Mycobacterial metabolism repression by MDP1)

    Enany Shymaa, 西山 晃史, 立石 善隆, 松本 壮吉

    感染症学雑誌   90 ( 臨増 )   303 - 303   2016.3

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  • マクロファージのHypoxia-inducible factor-1αによる結核菌の増殖調節機構

    岡 真優子, 尾関 百合子, 山口 雄大, 松本 壮吉

    日本細菌学雑誌   71 ( 1 )   151 - 151   2016.2

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  • 抗酸菌のタンパク質の抗原性と機能の分析(Analysis of antigenicity and functions of mycobacterial proteins)

    Enany Shymaa, 尾関 百合子, 西山 晃史, Savitskaya Anna, 立石 善隆, 阿戸 学, 山本 格, 松本 壮吉

    日本細菌学雑誌   71 ( 1 )   65 - 65   2016.2

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  • 結核・抗酸菌症に関する最近のprovocativeな研究 結核・抗酸菌の潜伏感染メカニズム

    松本 壮吉

    日本細菌学雑誌   71 ( 1 )   40 - 40   2016.2

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  • 結核・抗酸菌症に関する最近のprovocativeな研究 ルシフェラーゼ発現リコンビナントBCGによる新規結核薬の迅速スクリーニング系の確立と実践(Latest provocative studies on tuberculosis and mycobacterial infections A new screen for TB drug candidates utilizing a luciferase-expressing recombinant BCG)

    尾関 百合子, 山口 雄大, Enany Shymaa, 五十嵐 雅之, 西内 由紀子, 岡 真優子, 岩本 朋忠, 小椋 義俊, 林 哲也, 立石 善隆, 西山 晃史, 松本 壮吉

    日本細菌学雑誌   71 ( 1 )   40 - 40   2016.2

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  • 結核菌におけるポリフェノールの抗菌作用の検討

    立石 善隆, 尾関 百合子, 西山 晃史, 松本 壮吉

    日本細菌学雑誌   71 ( 1 )   139 - 139   2016.2

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  • 非結核性抗酸菌のバイオフィルム形成におけるGlycopeptidolipidの役割

    西内 由紀子, 戸谷 孝洋, 立石 善隆, 金子 幸弘, 松本 壮吉

    日本細菌学雑誌   71 ( 1 )   111 - 111   2016.2

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  • 潜在期結核菌抗原の精製と感染診断への応用

    西田 由貴子, 北所 健悟, 尾関 百合子, 立石 善隆, 井上 学, 仁木 満美子, 金子 幸弘, 松本 壮吉, 有坂 文雄, 森川 耿右, 津中 康央, 藤原 芳江, 片平 正人, 真嶋 司, 前倉 亮治

    日本細菌学雑誌   71 ( 1 )   105 - 105   2016.2

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  • 組換え結核菌抗原MDP1およびDNAアジュバントG9.1からなる結核ブースターワクチン候補の最適化の試み

    前山 順一, 山崎 利雄, 山本 十糸子, 林 大介, 鈴木 史子, 尾関 百合子, 伊保 澄子, 松本 壮吉, 山本 三郎, 網 康至, 須崎 百合子, 後藤 義孝

    日本細菌学雑誌   71 ( 1 )   99 - 99   2016.2

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  • HDLコレステロールはMycobacterium tuberculosisに感染したマクロファージからのサイトカインの産生を抑制する(HDL-cholesterol suppresses the production of cytokines from M. tuberculosis infected macrophages)

    井上 学, 仁木 満美子, 尾関 百合子, 岡 真優子, 凪 幸世, 一瀬 休生, 金子 幸弘, 濱野 真二郎, 松本 壮吉

    日本細菌学雑誌   71 ( 1 )   152 - 152   2016.2

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  • 結核菌の病原因子

    立石 善隆, 松本 壮吉

    呼吸器内科   29 ( 1 )   65 - 70   2016.1

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    Other Link： http://search.jamas.or.jp/link/ui/2016139494

  • 西ケニアビタ県の学童におけるマンソン住血吸虫の空間分布とその感染リスク要因について

    凪幸世, CHADEKA Evans, 砂原俊彦, MUTUNGI Faith, JUSTIN Yombo, K. Dan, 金子聰, 一瀬休生, 松本壮吉, NJENGA Sammy M, 橋爪真弘, 嶋田雅暁, 濱野真二郎

    日本熱帯医学会大会プログラム抄録集   56th   38   2015.12

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  • プロバイオティクス医療を視野に入れたヨーグルトの抗菌効果の検討

    田島 陽介, 岡部 康之, 立石 善隆, 西山 晃史, 尾関 百合子, 亀山 仁史, 松本 壮吉, 若井 俊文

    新潟医学会雑誌   129 ( 10 )   593 - 600   2015.10

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    Other Link： http://hdl.handle.net/10191/44215

  • 【持続感染・潜伏感染の機序と病態】 結核菌の潜伏感染に関わるメカニズムと新しい結核制御技術の可能性

    松本 壮吉, 西山 晃史, 尾関 百合子

    化学療法の領域   31 ( 9 )   1863 - 1870   2015.8

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  • バイオフィルム形成と環境中気体組成

    西内 由紀子, 戸谷 孝洋, 金子 幸弘, 松本 壮吉

    日本バイオフィルム学会学術集会プログラム・抄録集   29回   29 - 29   2015.7

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  • 高グルコースによる結核菌のNO抵抗性と増殖作用

    岡真優子, 大西愛, 石井美菜子, 尾関百合子, 松本壮吉, 三角和広, 市川寛, 南山幸子

    日本酸化ストレス学会学術集会プログラム・抄録集   68th   134   2015.5

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  • 非結核性抗酸菌のバイオフィルム形成時の特徴

    戸谷 孝洋, 西内 由紀子, 北中 博美, 金子 幸弘, 松本 壮吉

    BACTERIAL ADHERENCE & BIOFILM   28   49 - 52   2015.5

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  • 結核病期特異的CD4陽性T細胞性免疫応答の検討

    山下 嘉郎, 田中 健之, 小江 俊行, 川上 健司, 岡 真優子, 松本 壮吉, 寺原 和孝, 横田 恭子, 森本 浩之輔, 有吉 紅也

    日本呼吸器学会誌   4 ( 増刊 )   253 - 253   2015.3

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  • 肺結核特異抗原に対する液性免疫の評価

    星野 仁彦, 仁木 満美子, 鈴川 真穂, 赤司 俊介, 永井 英明, 大田 健, 森本 耕三, 倉島 篤行, 吉山 崇, 工藤 翔二, 松本 壮吉

    日本呼吸器学会誌   4 ( 増刊 )   254 - 254   2015.3

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  • 環境から分離した非結核性抗酸菌のバイオフィルム形成促進因子

    西内 由紀子, 金子 幸弘, 松本 壮吉

    結核   90 ( 2 )   372 - 372   2015.2

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  • LTBI症例における血清抗体を用いた前発病状態の検出

    藤川 健弥, 北田 清悟, 松本 壮吉, 前倉 亮治

    結核   90 ( 2 )   296 - 296   2015.2

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  • 結核免疫に及ぼす血清脂質の影響

    金子 幸弘, 井上 学, 仁木 満美子, 西内 由紀子, 掛屋 弘, 松本 壮吉

    結核   90 ( 2 )   264 - 264   2015.2

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  • 効果的なワクチン開発のための結核特異抗原に対する液性免疫の解析

    星野 仁彦, 仁木 満美子, 永井 英明, 吉山 崇, 森本 耕三, 仁木 誠, 金子 幸弘, 松本 壮吉, 倉島 篤行, 後藤 元, 工藤 翔二

    結核   90 ( 2 )   264 - 264   2015.2

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  • 結核菌組換えタンパク質MDP1およびCpG-DNAであるG9.1を用いた結核ブースターワクチンの開発

    前山 順一, 山崎 利雄, 山本 十糸子, 林 大介, 松本 壮吉

    日本細菌学雑誌   70 ( 1 )   235 - 235   2015.2

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  • HDL-cholesterolが結核菌感染に与える影響

    井上 学, 仁木 満美子, 岡 真優子, 尾関 百合子, 一瀬 休生, 金子 幸弘, 松本 壮吉

    日本細菌学雑誌   70 ( 1 )   229 - 229   2015.2

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  • M.aviumのバイオフィルム形成時の特徴

    戸谷 孝洋, 西内 由紀子, 金子 幸弘, 松本 壮吉

    日本細菌学雑誌   70 ( 1 )   142 - 142   2015.2

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  • 結核菌の増殖制御や潜在性結核の解析および、結核ワクチンの開発研究

    松本 壮吉

    臨牀と研究   92 ( 1 )   116 - 116   2015.1

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  • Unique cytokine profiles of CD4+T cell to Acr, HBHA and MDP-1 antigens in different clinical stage of mycobacterium tuberculosis infection

    Yoshiro Yamashita, Takeshi Tanaka, Toshiyuki Oe, Kenji Kawakami, Mayuko Oka, Sohkichi Matsumoto, Kazutaka Terahara, Yasuko Tsunetsugu-Yokota, Konosuke Morimoto, Koya Ariyoshi

    EUROPEAN RESPIRATORY JOURNAL   44   2014.9

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  • 非結核性抗酸菌のバイオフィルム形成時の特徴

    戸谷 孝洋, 西内 由紀子, 北中 博美, 金子 幸弘, 松本 壮吉

    Bacterial Adherence & Biofilm 学術集会   28回   36 - 36   2014.7

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  • 非結核性抗酸菌のバイオフィルム形成因子

    西内 由紀子, 戸谷 孝洋, 松本 壮吉

    BACTERIAL ADHERENCE & BIOFILM   27   49 - 52   2014.5

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  • 私達の研究 結核ワクチン開発の現状と新しい結核ワクチン開発に向けて

    松本 壮吉, 尾関 百合子

    化学療法の領域   30 ( 6 )   1283 - 1290   2014.5

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  • 肋骨BCG骨髄炎の一例

    戸田 彩季, 時政 定雄, 山下 加奈子, 趙 有季, 新宅 治夫, 瀬戸 俊之, 松本 壮吉

    小児感染免疫   26 ( 1 )   113 - 114   2014.4

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  • マクロファージの糖代謝酵素とグルコース濃度による結核菌の増殖制御(Glycolytic enzymes and glucose concentration in macrophages regulate the replication of Mycobacteria)

    今川 裕香子, 岡 真優子, 尾関 百合子, 松本 壮吉

    日本細菌学雑誌   69 ( 1 )   170 - 170   2014.2

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  • 細菌による持続感染の成立と発症の分水嶺 結核菌の潜伏感染機構と新しい結核制御の可能性

    松本 壮吉

    日本細菌学雑誌   69 ( 1 )   104 - 104   2014.2

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  • 非結核性抗酸菌のバイオフィルム形成解析

    戸谷 孝洋, 西内 由紀子, 松本 壮吉

    日本細菌学雑誌   69 ( 1 )   154 - 154   2014.2

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  • ケニア共和国クワレ地区小学生を対象とした潜在性結核感染と寄生虫感染の関連

    尾関 百合子, 武田 知芳里, 岡部 真裕子, 井上 学, 岡 真優子, 平山 幸雄, 一瀬 休生, 小林 和夫, 松本 壮吉, 濱野 真二郎, 松本 真, 織田 哲弥, 石田 英和, 嶋田 雅曉, Juma Mwatasa, Kinyua Faith, Chadeka Asena Evans

    日本細菌学雑誌   69 ( 1 )   140 - 140   2014.2

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  • Ethidium monoazideを利用した薬剤耐性抗酸菌の迅速検出法の開発

    仁木 誠, 仁木 満美子, 松本 壮吉

    日本細菌学雑誌   69 ( 1 )   140 - 140   2014.2

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  • 潜在性結核および内因性再燃の検出を目的とした血清診断法の開発

    仁木 満美子, 仁木 誠, 松本 壮吉, 星野 仁彦

    日本細菌学雑誌   69 ( 1 )   140 - 140   2014.2

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  • 結核菌組換えタンパク質およびTLR9リガンドを用いた結核ブースターワクチンの結核菌噴霧感染による評価

    前山 順一, 山崎 利雄, 山本 十糸子, 林 大介, 松本 壮吉, 網 康至, 須崎 百合子, 伊保 澄子, 山本 三郎

    日本細菌学雑誌   69 ( 1 )   250 - 250   2014.2

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  • 【抗酸菌感染症】 抗酸菌の細菌学的特徴と病原性

    西内 由紀子, 松本 壮吉

    感染症内科   2 ( 1 )   8 - 14   2014.1

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  • 結核とその制圧を目指した研究

    松本 壮吉

    新潟県医師会報   ( 766 )   2 - 7   2014.1

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  • TLR9リガンドであるG9.1をアジュバントとして用いた結核ブースターワクチンの開発

    前山順一, 山崎利雄, 山本十糸子, 林大介, 尾関百合子, 松本壮吉, 伊保澄子, 山本三郎

    日本ワクチン学会学術集会プログラム・抄録集   18th   189   2014

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  • 潜在性抗酸菌感染症の病態機構の解明及び診断・治療・予防に関する研究 潜在性結核の成立を担う菌と宿主双方の分子とその機能解明に関する研究

    松本壮吉, 岡真優子, 王亜軍, 仁木満美子, 仁木誠, 平山幸雄, 尾関百合子, 大原直也, 辻村邦夫, 小出幸夫, 北田清悟, 前倉亮治, 阿戸学, 小林和夫

    潜在性抗酸菌感染症の病態機構の解明及び診断・治療・予防に関する研究 平成23-25年度 総合研究報告書   17 - 26   2014

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  • 潜在性抗酸菌感染症の病態機構の解明及び診断・治療・予防に関する研究 潜在性結核の成立を担う菌と宿主双方の分子とその機能解明に関する研究

    松本壮吉, 岡真優子, 王亜軍, 平山幸雄, 仁木満美子, 尾関百合子, 大原直也, 辻村邦夫, 小出幸夫, 北田清吾, 前倉亮治, 阿戸学, 小林和夫

    潜在性抗酸菌感染症の病態機構の解明及び診断・治療・予防に関する研究 平成25年度 総括・分担研究報告書   15 - 20   2014

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  • Risk Factors and Spatial Distribution of Schistosoma mansoni Infection among Primary School Children in Mbita District, Western Kenya

    NAGI Sachiyo, CHADEKA Evans A., SUNAHARA Toshihiko, CHAVES Luis Fernando, MUTUNGI Faith, DAN Yombo Justin K., KANEKO Satoshi, ICHINOSE Yoshio, MATSUMOTO Sohkichi, NJENGA Sammy M., HASHIZUME Masahiro, SHIMADA Masaaki, HAMANO Shinjiro

    日本寄生虫学会大会プログラム・抄録集   83rd   2014

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  • 抗酸菌の休眠現象や薬剤抵抗性に関わる分子メカニズム 抗酸菌の休眠と薬剤耐性機構

    松本 壮吉

    日本ハンセン病学会雑誌   82 ( 3 )   119 - 122   2013.12

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  • 潜在性結核のバイオマーカーとしての抗Antigen85およびMycobacteri DNA‐binding protein1抗体

    岡真優子, 立石善隆, 平山幸雄, 尾関百合子, 前倉亮次, 小林和夫, 松本壮吉

    日本熱帯医学会大会プログラム抄録集   54th   130   2013.9

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  • ケニア共和国Mbita地区の児童における結核菌感染と鉤虫感染の関連

    井上学, 岡真優子, 仁木満美子, 尾関百合子, 一ノ瀬休生, 濱野真二郎, 松本壮吉

    日本熱帯医学会大会プログラム抄録集   54th   129 - 130   2013.9

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  • 【結核-病態解明と制御の新展開】 潜在性結核と結核菌の潜伏感染メカニズム 結核菌の潜伏感染機構

    松本 壮吉

    医学のあゆみ   246 ( 6-7 )   470 - 473   2013.8

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  • 非結核性抗酸菌のバイオフィルム形成因子

    西内 由紀子, 戸谷 孝洋, 松本 壮吉

    Bacterial Adherence & Biofilm 学術集会   27回   42 - 42   2013.7

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  • ケニア国の小学生を対象とした結核菌抗原に対する宿主応答の解析

    岡真優子, 松本壮吉, 尾関百合子

    長崎大学熱帯医学研究拠点共同研究報告集   2012   143 - 147   2013.7

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  • 結核菌感染に対するマクロファージの生体防御機構

    岡真優子, 松本壮吉, 尾関百合子, 市川寛, 南山幸子

    日本酸化ストレス学会学術集会プログラム・抄録集   66th   92   2013.6

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  • 再考!バイオフィルム! 結核菌の増殖、長期生存、および静止期以降の薬剤抵抗性獲得の分子メカニズム

    松本 壮吉

    BACTERIAL ADHERENCE & BIOFILM   26   21 - 24   2013.5

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  • 非結核性抗酸菌が形成するバイオフィルムの生態学的特徴

    西内 由紀子, 戸谷 孝洋, 立石 善隆, 松本 壮吉

    BACTERIAL ADHERENCE & BIOFILM   26   37 - 40   2013.5

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  • 抗酸菌に対する生体防御反応と発症予防方策の開発戦略 抗酸菌の潜伏感染や薬剤抵抗性に関わる分子メカニズム

    松本 壮吉

    日本ハンセン病学会雑誌   82 ( 1-2 )   15 - 15   2013.4

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  • 結核関連抗原に対するCD4陽性T細胞サイトカインプロファイルの検討

    山下 嘉郎, 星野 仁彦, 岡 真優子, 松本 壮吉, 有賀 晴之, 横田 恭子, 有吉 紅也

    日本内科学会雑誌   102 ( Suppl. )   179 - 179   2013.2

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  • リコンビナントBCG(rBCG)を用いた迅速スクリーニング法による抗結核薬の探索と同定

    尾関 百合子, 西内 由紀子, 小椋 義俊, 岩本 朋忠, 林 哲也, 岡 真優子, 仁木 満美子, 立石 善隆, 平山 幸雄, 松本 壮吉

    日本細菌学雑誌   68 ( 1 )   181 - 181   2013.2

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  • 高病原性非結核性抗酸菌臨床菌株のゲノムシーケンス(Draft Genome Sequence of A Hypervirulent Clinical Mycobacterium intracellulare Strain)

    立石 善隆, 平山 幸雄, 尾関 百合子, 西内 由紀子, 仁木 満美子, 小椋 義俊, 林 哲也, 小林 和夫, 松本 壮吉

    日本細菌学雑誌   68 ( 1 )   176 - 176   2013.2

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  • 環境分離抗酸菌のバイオフィルム形成因子の検討

    戸谷 孝洋, 西内 由紀子, 立石 善隆, 松本 壮吉

    日本細菌学雑誌   68 ( 1 )   135 - 135   2013.2

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  • BCG Tokyo172株のサブポピュレーションBCG-IIを用いた結核ブースターワクチン候補の評価

    前山 順一, 伊保 澄子, 岡 真優子, 井坂 雅徳, 松本 壮吉, 山本 三郎

    日本細菌学雑誌   68 ( 1 )   207 - 207   2013.2

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  • ケニア共和国における学生の結核菌感染とhookworm感染の関連

    井上 学, 岡 真優子, 仁木 満美子, 尾関 百合子, 一瀬 休生, 小林 和夫, 松本 壮吉

    日本細菌学雑誌   68 ( 1 )   219 - 219   2013.2

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  • 潜在性結核患者の血清中での結核菌抗原に対するイムノグロブリンg(Antigen 85A and Mycobacterial DNA-binding protein 1 are targets of IgG in past tuberculosis)

    岡 真優子, 立石 善隆, 平山 幸雄, 尾関 百合子, 小林 和夫, 松本 壮吉

    日本細菌学雑誌   68 ( 1 )   214 - 214   2013.2

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  • ケニア西部の小学生における寄生虫感染とリスク要因に関する研究

    凪幸世, CHADEKA Evans, MUTUNGI Faith, KALENDA Yombo, 伊藤誠, 嶋田雅暁, 一瀬休生, 金子聡, 松本壮吉, NJENGA Sammy, 砂原俊彦, 橋爪真弘, 濱野真二郎

    日本寄生虫学会大会プログラム・抄録集   82nd   81   2013.2

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  • 私達の研究 鉄代謝およびイソニアジド耐性にかかわる結核菌分子の機能と治療法開発の可能性

    仁木 満美子, 松本 壮吉

    化学療法の領域   29 ( 2 )   301 - 306   2013.1

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  • 国際共同基盤研究に応用する抗酸菌感染症研究の整備 結核病態に関する分子生物学的研究

    松本壮吉, 井上学, 仁木満美子, 濱野真二郎, 嶋田雅曉, 一瀬休生, 凪幸世, 岡真優子, 尾関百合子, 岡部真裕子, 小林和夫, 野内英樹, 原田登之

    国際共同基盤研究に応用する抗酸菌感染症研究の整備 平成24年度 総括・分担研究報告書   83 - 87   2013

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  • 潜在性抗酸菌感染症の病態機構の解明及び診断・治療・予防に関する研究 潜在性結核の成立を担う菌と宿主双方の分子とその機能解明

    松本壮吉, 井上学, 仁木満美子, 濱野真二郎, 嶋田雅暁, 一瀬休生, 凪幸世, 岡真優子, 尾関百合子, 岡部真裕子, 小林和夫

    潜在性抗酸菌感染症の病態機構の解明及び診断・治療・予防に関する研究 平成24年度 総括・分担研究報告書   15 - 19   2013

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  • ケニア西部の小学生における寄生虫感染率とリスク要因の解析

    凪幸世, EVANS Chadeka, FAITH Mutungi, YOMBO Kalenda Dan Justin, 伊藤誠, 金子聡, 一瀬休生, 嶋田雅暁, 松本壮吉, SAMMY Njenga, 濱野真二郎

    Journal of Epidemiology   23 ( Supplement 1 )   2013

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  • BCGの効果判定方法

    平山 幸雄, 松本 壮吉

    日本医事新報   ( 4627 )   98 - 99   2012.12

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  • 結核菌感染を診断するバイオマーカー

    岡 真優子, 尾関 百合子, 松本 壮吉, 岩尾 洋

    大阪市医学会雑誌   61 ( 3-4 )   81 - 87   2012.12

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    Other Link： http://search.jamas.or.jp/link/ui/2013189878

  • ケニア共和国における,学生の潜在性結核菌感染と様々な寄生虫感染

    井上学, 岡真優子, 仁木満美子, 尾関百合子, 小野賢司, 松本真, 凪幸世, KALENDA Yombo, Dan Justin, 濱野真二郎, 一瀬休生, 小林和夫, 松本壮吉

    日本熱帯医学会大会プログラム抄録集   53rd   83   2012.9

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  • 細菌付着の制御とBiofilm形成 非結核性抗酸菌が形成するバイオフィルムの生態学的特徴

    西内 由紀子, 戸谷 孝洋, 立石 善隆, 前倉 亮治, 松本 壮吉

    Bacterial Adherence & Biofilm 学術集会   26回   25 - 25   2012.7

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  • 再考!バイオフィルム 結核菌の増殖、長期生存、および静止期以降の薬剤抵抗性獲得の分子メカニズム

    松本 壮吉

    Bacterial Adherence & Biofilm 学術集会   26回   20 - 21   2012.7

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  • 結核―その病態,診断,治療,感染対策 基礎各論 新しい結核ワクチン開発の展望

    松本壮吉, 尾関百合子, 小林和夫

    臨床と微生物   39 ( 2 )   131 - 136   2012.3

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  • マクロファージのグルコース代謝と宿主内結核菌の増殖

    岡真優子, 合田亘人, 曽我朋義, 尾関百合子, 小林和夫, 松本壮吉, 岩尾洋

    日本細菌学雑誌   67 ( 1 )   104   2012.2

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  • 休眠時における抗酸菌の遺伝子発現解析

    仁木 満美子, 仁木 誠, 小林 和夫, 松本 壮吉

    日本細菌学雑誌   67 ( 1 )   150 - 150   2012.2

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  • Mycobacterial DNA-binding protein 1(MDP1)に見いだされたFerritin-super family蛋白質様活性

    松本 壮吉, 岡 真優子, 西内 由紀子, 仁木 満美子, 尾関 百合子, 立石 善隆, 小林 和夫, 高塚 正樹, 佐藤 英介, 井上 正康

    日本細菌学雑誌   67 ( 1 )   149 - 149   2012.2

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  • ケニアの学生における、結核菌タンパク質に対する免疫応答の分析

    井上 学, 岡 真優子, 仁木 満美子, 尾関 百合子, 一瀬 休生, 小林 和夫, 松本 壮吉, 濱野 真二郎, 凪 幸世, Kalenda Yombo, 嶋田 雅暁, 小野 賢司, 松本 真, Njenga Sammy

    日本細菌学雑誌   67 ( 1 )   129 - 129   2012.2

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  • 高病原性Mycobacterium intracellulare臨床分離株のドラフトゲノム解析

    立石 善隆, 小椋 義俊, 平山 幸雄, 尾関 百合子, 西内 由紀子, 仁木 満美子, 林 哲也, 小林 和夫, 松本 壮吉, 王 亜軍, 北田 清悟, 前倉 亮治

    日本細菌学雑誌   67 ( 1 )   119 - 119   2012.2

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  • マウスモデルにおけるBCGワクチン効果の減衰に関する研究(Loss of anti-mycobacterial efficacy in mice over time following vaccination with BCG)

    尾関 百合子, 平山 幸雄, 岡 真優子, 立石 善隆, 瀧井 猛将, 山本 三郎, 小林 和夫, 松本 壮吉

    日本細菌学雑誌   67 ( 1 )   158 - 158   2012.2

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  • 定常期抗酸菌にみられるイソニアジド抵抗性の解析

    仁木 誠, 仁木 満美子, 小林 和夫, 松本 壮吉, 切替 照雄

    日本細菌学雑誌   67 ( 1 )   150 - 150   2012.2

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  • 結核研究の最先端 潜在性結核の分子機構と結核制圧研究

    松本 壮吉, 岡 真優子, 北田 清悟, 前倉 亮治, 小林 和夫

    日本医学会総会会誌   28回 ( II )   67 - 67   2011.10

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  • マクロファージのLPS応答におけるミトコンドリアの役割

    笠原 恵美子, 関山 敦生, 堀 美香, 松本 壮吉, 佐藤 英介, 岡村 春樹, 井上 正康, 北川 誠一

    日本生化学会大会プログラム・講演要旨集   84回   4P - 0535   2011.9

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  • 結核菌の休眠現象と潜在性結核

    松本 壮吉, 小林 和夫

    日本生化学会大会プログラム・講演要旨集   84回   1S9a - 5   2011.9

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  • 環境から分離したMycobacterium aviumのバイオフィルム形成

    西内 由紀子, 松本 壮吉, 立石 善隆, 北田 清悟, 前倉 亮治

    結核   86 ( 3 )   374 - 374   2011.3

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  • 抗酸菌検査の進歩 結核血清診断の進歩

    立石 善隆, 北田 清悟, 松本 壮吉, 前倉 亮治

    結核   86 ( 3 )   310 - 310   2011.3

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  • 結核研究の新たな展開：潜在性結核と結核菌—休眠現象の分子メカニズム

    仁木 満美子, 尾関 百合子, 岡 真優子, 松本 壮吉

    最新医学   66 ( 3 )   2011

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  • Global Threats and the Control of Multidrug-resistant tuberculosis

    Kazuo Kobayashi, Manabu Ato, Sohkichi Matsumoto

    Journal of Disaster Research   6 ( 4 )   443 - 450   2011

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    DOI： 10.20965/jdr.2011.p0443

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  • 【環境、生態の変動と感染症】 生活環境における非結核性抗酸菌の分布

    西内 由紀子, 立石 善隆, 松本 壮吉

    化学療法の領域   26 ( 12 )   2405 - 2413   2010.11

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  • 抗酸菌感染症における感染制御の進歩

    松本 壮吉

    感染症学雑誌   84 ( 4 )   489 - 489   2010.7

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  • 抗酸菌感染症における感染制御の進歩

    松本 壮吉

    感染症学雑誌   84 ( 臨増 )   100 - 100   2010.3

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  • 結核菌感染における制御性T細胞の関与

    尾関 百合子, 菅原 勇, 岡 真優子, 小林 和夫, 松本 壮吉

    日本細菌学雑誌   65 ( 1 )   189 - 189   2010.2

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  • 病原性の起源を生態系の視点から考える 自然環境生息菌をモデルとして 生活環境由来Mycobacterium avium complexの遺伝子多型解析

    西内 由紀子, 松本 壮吉, 立石 善隆

    日本細菌学雑誌   65 ( 1 )   91 - 91   2010.2

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  • 潜在性結核の診断法の確立に向けた臨床への橋渡し研究(第1報)

    岡 真優子, 平山 幸雄, 立石 善隆, 小林 和夫, 松本 壮吉

    日本細菌学雑誌   65 ( 1 )   198 - 198   2010.2

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  • 抗酸菌感染症の発症・診断・治療・新世代予防技術に係わる分子機構に関する研究 結核菌潜伏感染の分子機構と治療・予防戦略

    小林和夫, 前倉亮治, 北田清悟, 松本壮吉, 藤原永年, 阿戸学, 大西和夫, 高橋宜聖, 岡部真裕子, 大原直也

    抗酸菌感染症の発症・診断・治療・新世代予防技術に係わる分子機構に関する研究 平成21年度 総括・分担研究報告書   17 - 21   2010

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  • MLPA法による多剤耐性結核菌の検出

    田丸 亜貴, 河原 隆二, 松本 壮吉, 鈴木 定彦

    結核   84 ( 5 )   397 - 397   2009.5

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  • 集団感染事例におけるVNTR型とIS6110-RFLPパターンの比較

    田丸 亜貴, 松本 壮吉

    結核   84 ( 5 )   386 - 386   2009.5

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  • 肺Mycobacteirum avium complex症患者由来M.aviumと豚由来M.aviumの血清型比較

    西内 由紀子, 田栗 貴博, 松本 壮吉, 立石 善隆, 北田 清悟, 田丸 亜貴, 鈴木 定彦, 前倉 亮治

    結核   84 ( 5 )   409 - 409   2009.5

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  • 環境改変と感染症 生活環境に分布するMycobacterium avium complexと臨床分離株の多型解析

    西内 由紀子, 松本 壮吉, 立石 善隆, 鈴木 定彦

    日本細菌学雑誌   64 ( 1 )   96 - 96   2009.2

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  • 抗結核薬スクリーニング系の確立と実践

    尾関 百合子, 原田 誠, 西内 由紀子, 山本 三郎, 小林 和夫, 松本 壮吉, 五十嵐 雅之, 木下 直子, 田丸 亜貴

    日本細菌学雑誌   64 ( 1 )   193 - 193   2009.2

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  • 抗酸菌の薬剤感受性におけるMDP1の調節機構の解析

    仁木 誠, 吉村 満美子, 小林 和夫, 松本 壮吉

    日本細菌学雑誌   64 ( 1 )   192 - 192   2009.2

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  • DNAワクチンを用いたMycobacterium DNA-binding protein 1(MDP1)のマウスT細胞エピトープの同定

    鈴木 大介, 永田 年, 辻村 邦夫, 松本 壮吉, 小出 幸夫

    日本細菌学雑誌   64 ( 1 )   192 - 192   2009.2

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  • 抗酸菌感染症研究における新たな視点 結核菌の増殖に対するヒアルロン酸の作用

    平山 幸雄, 吉村 満美子, 尾関 百合子, 菅原 勇, 小林 和夫, 松本 壮吉, 木全 弘治, 板野 直樹, 青木 俊明

    日本細菌学雑誌   64 ( 1 )   93 - 93   2009.2

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  • 抗酸菌感染症研究における新たな視点 急速な臨床経過に合致した高病原性Mycobacterium avium-intracellulare complex菌株の同定

    立石 善隆, 平山 幸雄, 尾関 百合子, 西内 由紀子, 吉村 満美子, 小林 和夫, 松本 壮吉, 北田 清悟, 前倉 亮治

    日本細菌学雑誌   64 ( 1 )   93 - 93   2009.2

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  • 結核の生物学から結核対策の進歩まで 抗酸菌の蛋白質機能から分子病態まで(Tuberculosis, from biology to development of control strategies From the functions of a protein to molecular pathogenesis of mycobacteria)

    松本 壮吉, 小林 和夫

    日本細菌学雑誌   64 ( 1 )   43 - 43   2009.2

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  • 結核菌感染マクロファージにおけるhypoxia-inducible factor-1alphaの作用機構

    岡 真優子, 小林 和夫, 松本 壮吉

    日本細菌学雑誌   64 ( 1 )   190 - 190   2009.2

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  • Mycobacterium intracellulare由来血清型7,12,13型糖ペプチド脂質の構造類似性とオリゴ糖解析

    藤原 永年, 中田 登, 中田 崇, 水野 淨子, 合田 麗奈, 牧野 正彦, 吉村 満美子, 松本 壮吉, 前田 伸司

    日本細菌学雑誌   64 ( 1 )   188 - 188   2009.2

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  • 抗酸菌感染症の発症・診断・治療・新世代予防技術に係わる分子機構に関する研究 結核菌潜伏感染の分子機構と治療・予防戦略

    小林和夫, 前倉亮治, 北田清悟, 松本壮吉, 藤原永年, 大原直也, 阿戸学, 大西和夫, 高橋宜聖, 岡部真裕子

    抗酸菌感染症の発症・診断・治療・新世代予防技術に係わる分子機構に関する研究 平成20年度 総括・分担研究報告書   15 - 19   2009

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  • 【結核】 結核ワクチン研究の現状と展望

    松本 壮吉, 小林 和夫

    臨床検査   52 ( 10 )   1149 - 1153   2008.10

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    Other Link： http://search.jamas.or.jp/link/ui/2008350771

  • 抗酸菌の薬剤感受性におけるMDP1の調節機構の解析

    仁木 誠, 吉村 満美子, 和田 崇之, 小林 和夫, 松本 壮吉

    結核   83 ( 3 )   342 - 342   2008.3

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  • Mycobacterial DNA-binding protein 1(MDP1)による増殖と細胞壁合成の同調メカニズム

    松本 壮吉, 尾関 百合子, 西内 由紀子, 藤原 永年, 吉村 満美子, 小林 和夫

    結核   83 ( 3 )   341 - 341   2008.3

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  • BCG亜株の脂質生化学的比較研究

    藤原 永年, 瀧井 猛将, 藤田 由希子, 矢野 郁也, 前田 伸司, 松本 壮吉, 山本 三郎

    結核   83 ( 3 )   293 - 293   2008.3

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  • 肺Mycobacterium avium complex(MAC)症患者の家庭浴室に常在するMACと喀痰分離株の多型解析

    西内 由紀子, 田丸 亜貴, 北田 清悟, 田栗 貴博, 松本 壮吉, 立石 善隆, 前倉 亮治

    結核   83 ( 3 )   289 - 289   2008.3

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  • 家庭浴室由来Mycobacterium avium complexの多型性と臨床分離株との相同性

    西内 由紀子, 松本 壮吉, 立石 善隆, 田丸 亜貴, 前倉 亮治, 北田 清悟, 田栗 貴博

    日本細菌学雑誌   63 ( 1 )   163 - 163   2008.2

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  • 抗酸菌の遺伝子発現および薬剤感受性におけるMDP1の役割

    仁木 誠, 吉村 満美子, 和田 崇之, 小林 和夫, 松本 壮吉

    日本細菌学雑誌   63 ( 1 )   183 - 183   2008.2

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  • 抗酸菌における増殖と細胞壁合成の同調機構

    松本 壮吉, 奥山 めぐみ, 尾関 百合子, 内藤 真理子, 西内 由紀子, 藤原 永年, 吉村 満美子, 小林 和夫, 勝部 智也, 高塚 正樹, 坪井 敬文

    日本細菌学雑誌   63 ( 1 )   181 - 181   2008.2

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  • 結核病巣におけるヒアルロン酸の産生と局在

    平山 幸雄, 吉村 満美子, 尾関 百合子, 菅原 勇, 青木 俊明, 西内 由紀子, 小林 和夫, 松本 壮吉, 木全 弘治, 板野 直樹

    日本細菌学雑誌   63 ( 1 )   88 - 88   2008.2

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  • 結核菌感染における制御性T細胞の役割(2)

    尾関 百合子, 小林 和夫, 松本 壮吉, 久枝 一, 菅原 勇, 宇田川 忠, 青木 俊明, 田村 敏生

    日本細菌学雑誌   63 ( 1 )   157 - 157   2008.2

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  • Mycobacterium intracellulare由来血清型7,12型glycopeptidolipid糖鎖合成遺伝子の機能解析

    藤原 永年, 中田 登, 前田 伸司, 中 崇, 水野 淨子, 牧野 正彦, 松本 壮吉, 矢野 郁也

    日本細菌学雑誌   63 ( 1 )   97 - 97   2008.2

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  • 【変貌する細菌感染症】 結核における特異性炎の形成メカニズムと結核対策研究の現在 結核菌感染症

    松本 壮吉

    医学のあゆみ   223 ( 8 )   611 - 614   2007.11

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  • 抗酸菌研究の最前線 結核菌病原因子による病変形成と感染防御

    松本 壮吉, 小林 和夫

    結核   82 ( 10 )   786 - 789   2007.10

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  • 肺Mycobacterium avium complex(MAC)症患者の家庭浴室内におけるMACの検出

    西内 由紀子, 田丸 亜貴, 北田 清悟, 田栗 貴博, 前倉 亮治, 松本 壮吉, 鈴木 定彦

    結核   82 ( 4 )   439 - 439   2007.4

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  • 抗酸菌の蛋白質発現と薬剤抵抗性におけるMDP1の役割

    仁木 誠, 吉村 満美子, 平山 幸雄, 松本 壮吉, 和田 崇之, 小林 和夫

    結核   82 ( 4 )   403 - 403   2007.4

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  • 結核菌糖脂質の合成制御におけるmycobacterial DNA-binding protein 1(MDP1)の役割

    松本 壮吉, 藤原 永年, 吉村 満美子, 尾関 百合子, 西内 由紀子, 和田 崇之, 小林 和夫

    結核   82 ( 4 )   402 - 402   2007.4

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  • 日本国内の北京型結核菌に見られる遺伝的特異性

    和田 崇之, 長谷 篤, 前田 伸司, Shi Ruiru, 菅原 勇, 松本 壮吉, 岩本 朋忠

    結核   82 ( 4 )   372 - 372   2007.4

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  • 抗酸菌研究の最前線 結核菌病原因子による病変形成と感染防御

    松本 壮吉, 小林 和夫

    結核   82 ( 4 )   332 - 332   2007.4

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  • BCG感染時におけるTh1/Th2バランスへのSTAT6の役割

    尾関 百合子, 松本 壮吉, 小林 和夫

    結核   82 ( 4 )   406 - 406   2007.4

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  • ヒアルロン酸の抗酸菌増殖に対する作用

    平山 幸雄, 吉村 満美子, 仁木 誠, 松本 壮吉, 尾関 百合子, 菅原 勇, 青木 俊明, 和田 崇之, 西内 由紀子, 小林 和夫

    結核   82 ( 4 )   404 - 404   2007.4

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  • ミコール酸分子種の異なるcord factorの宿主応答

    藤原 永年, 松本 壮吉, 前田 伸司, 矢野 郁也, 小林 和夫

    結核   82 ( 4 )   403 - 403   2007.4

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  • 結核菌の新規病原因子MDP1の感染病態への関わり

    松本 壮吉, 尾関 百合子, 小林 和夫

    感染・炎症・免疫   37 ( 1 )   98 - 101   2007.3

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  • 抗酸菌の増殖に対するヒアルロン酸の作用

    平山幸雄, 吉村満美子, 尾関百合子, 菅原勇, 青木俊明, 和田嵩之, 西内田紀子, 小林和夫, 松本壯吉

    日本細菌学雑誌   62 ( 1 )   117 - 117   2007.2

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  • 家庭浴室のMycobacterium avium complexの検出 培養法、PCR法およびLAMP法の比較

    西内 由紀子, 松本 壮吉, 鈴木 定彦

    日本細菌学雑誌   62 ( 1 )   178 - 178   2007.2

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  • 結核菌の細胞壁合成におけるmycobacterial DNA-binding protein 1(MDP1)の役割

    松本 壮吉, 奥山 めぐみ, 尾関 百合子, 内藤 真理子, 西内 由紀子, 藤原 永年, 吉村 満美子, 和田 崇之, 小林 和夫

    日本細菌学雑誌   62 ( 1 )   91 - 91   2007.2

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  • 休眠期抗酸菌の薬剤抵抗性におけるMDP1の役割

    仁木 誠, 吉村 満美子, 和田 崇之, 小林 和夫, 松本 壮吉

    日本細菌学雑誌   62 ( 1 )   151 - 151   2007.2

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  • 新規抗結核薬OPC-67683の抗菌活性に関わる分子同定の試み

    奥山 めぐみ, 川崎 昌則, 松本 真, 小林 和夫, 松本 壮吉

    日本細菌学雑誌   62 ( 1 )   151 - 151   2007.2

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  • 【新感染症学 新時代の基礎・臨床研究】 感染症学総論 慢性化、潜伏化、再発再燃の機序 結核菌の潜伏感染と内因性再燃の分子機構

    松本 壮吉, 平山 幸雄, 小林 和夫

    日本臨床   65 ( 増刊2 新感染症学(上) )   124 - 128   2007.2

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    Other Link： http://search.jamas.or.jp/link/ui/2007232474

  • BCG感染におけるSTAT6の役割

    尾関 百合子, 小林 和夫, 松本 壮吉

    日本細菌学雑誌   62 ( 1 )   169 - 169   2007.2

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  • Molecular mechanisms of persistent infection with mycobacterium tuberculosis and reactivation

    Sohkichi Matsumoto, Yukio Hirayama, Kazuo Kobayashi

    Nippon rinsho. Japanese journal of clinical medicine   65   124 - 128   2007

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  • Priming-boosting vaccination with recombinant Mycobacterium bovis bacillus Calmette-Guerin and a nonreplicating vaccinia virus recombinant leads to long-lasting and effective immunity (vol 79, pg 12871, 2005)

    Yasushi Ami, Yasuyuki Izumi, Kazuhiro Matsuo, Kenji Someya, Masaru Kanekiyo, Shigeo Horibata, Naoto Yoshino, Koji Sakai, Katsuaki Shinohara, Sohkichi Matsumoto, Takeshi Yamada, Shudo Yamazaki, Naoki Yamamoto, Mitsuo Honda

    JOURNAL OF VIROLOGY   80 ( 20 )   10288 - 10288   2006.10

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  • Molecular mechanisms of persistent infection and adherence/entry to host cells with Mycobacterium tuberculosis for the development of a novel therapeutic and prophylactic intervention

    MATSUMOTO Sohkichi

    Zeitschrift der Japanischen Mikrobiologische Gesellschaft   61 ( 3 )   345 - 352   2006.8

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    DOI： 10.3412/jsb.61.345

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  • 微生物学の進歩 結核菌の潜伏感染と宿主細胞接着・侵入の分子機序 分子標的療法の開発を目指して

    松本 壮吉

    日本細菌学雑誌   61 ( 3 )   345 - 352   2006.8

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  • 抗酸菌のヒトマクロファージ様細胞(THP1)感染におけるグリコサミノグリカンの役割

    平山 幸雄, 松本 壮吉, 仁木 誠, 尾関 百合子, 西内 由紀子, 小林 和夫

    結核   81 ( 3 )   246 - 246   2006.3

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  • Mycobacterial DNA-binding protein 1の機能解析

    仁木 誠, 松本 壮吉, 平山 幸雄, 尾関 百合子, 西内 由起子, 小林 和夫

    結核   81 ( 3 )   249 - 249   2006.3

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  • 結核菌の病原性と制御性T細胞(CD4+CD25+Regulatory T細胞)の役割

    尾関 百合子, 松本 壮吉, 小林 和夫, 菅原 勇, 宇田川 忠, 青木 俊明, 久枝 一

    日本細菌学雑誌   61 ( 1 )   92 - 92   2006.2

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  • 結核菌DNAによるDNA結合性蛋白質の抗原性修飾

    松本 壮吉, 松本 真, 梅森 清子, 尾関 百合子, 山本 三郎, 山田 毅, 小林 和夫, 古堅 誠, 富重 辰夫, 平山 幸雄

    日本細菌学雑誌   61 ( 1 )   92 - 92   2006.2

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  • モルモット肺結核モデルにおける結核免疫の解析とサイトカイン/ケモカインアッセイ系の確立

    山本 三郎, 佐藤 由紀夫, 伊保 澄子, 後藤 義孝, 松本 壮吉, David N. McMurray

    財団法人ヒューマンサイエンス新興財団編：平成17年度創薬等ヒューマンサイエンス研究 国際共同研究事業 研究報告書   79 - 88   2006

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  • 結核菌の潜伏感染と内因性再燃の分子機構

    松本 壮吉

    化学療法の領域   21 ( 5 )   709 - 715   2005.4

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  • Mycobacterium avium-intracellulare complexのNO耐性解析

    西内 由紀子, 松本 壮吉

    結核   80 ( 3 )   266 - 266   2005.3

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  • 抗酸菌の肺胞上皮細胞侵入におけるMycobacterial DNA-binding protein1(MDP1)とヒアルロン酸の役割

    平山 幸雄, 松本 壮吉, 小林 和夫, 和田 崇之, 尾関 百合子, 西内 由起子, 山本 三郎

    結核   80 ( 3 )   268 - 268   2005.3

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  • 制御性T細胞(CD4+CD25+Regulatory T細胞)の結核菌感染における役割

    尾関 百合子, 松本 壮吉, 小林 和夫, 菅原 勇, 宇田川 忠

    結核   80 ( 3 )   267 - 267   2005.3

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  • 結核菌のヒストン様蛋白質Mycobacterial DNA-binding protein 1の抗原性におけるDNA介在の意義

    松本 壮吉, 小林 和夫, 松本 真, 尾関 百合子, 山本 三郎, 山田 毅

    結核   80 ( 3 )   266 - 266   2005.3

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  • 結核菌の核酸結合性蛋白質とDNAの複合体に対する免疫応答解析

    松本 壮吉, 松本 真, 梅森 清子, 尾関 百合子, 山本 三郎, 山田 毅, 小林 和夫

    日本細菌学雑誌   60 ( 1 )   157 - 157   2005.2

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  • 結核菌感染における制御性T細胞(CD4+CD25+ Regulatory T細胞)の役割

    尾関 百合子, 松本 壮吉, 小林 和夫

    日本細菌学雑誌   60 ( 1 )   156 - 156   2005.2

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  • 結核菌の肺胞上皮細胞への接着/侵入における,ヒアルロン酸-MDP1結合の役割

    平山 幸雄, 松本 壮吉, 和田 崇之, 尾関 百合子, 梅森 清子, 山本 三郎, 西内 由紀子, 松本 真, 小林 和夫

    日本細菌学雑誌   60 ( 1 )   104 - 104   2005.2

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  • 結核基礎研究の最前線 結核菌潜伏感染の分子機構と新規治療戦略

    松本 壮吉

    結核   79 ( 8 )   490 - 492   2004.8

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  • 抗酸菌の肺胞上皮細胞接着/侵入におけるグリコサミノグリカンの役割

    平山 幸雄, 松本 壮吉, 西内 由起子, 小林 和夫

    結核   79 ( 3 )   279 - 279   2004.3

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  • 結核基礎研究の最前線 結核菌潜伏感染の分子機構と新規治療戦略

    松本 壮吉

    結核   79 ( 3 )   163 - 163   2004.3

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  • 抗酸菌の肺胞上皮細胞接着における分子機構

    平山 幸雄, 松本 壮吉, 青木 圭子, 和田 崇之, 尾関 百合子, 松本 真, 小林 和夫

    日本細菌学雑誌   59 ( 1 )   184 - 184   2004.2

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  • 【食中毒】 海外旅行と食中毒

    松本 壮吉, 小林 和夫

    医薬ジャーナル   39 ( 5 )   1479 - 1483   2003.5

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  • 新しい結核ワクチンの開発とELISPOT assay(自動解析)を用いたT細胞活性化によるワクチン効果の解析

    田中 高生, 喜多 洋子, 井上 義一, 坂谷 光則, 岡田 全司, 桑山 さち子, 村木 裕美子, 稲永 由紀子, 金丸 典子, 橋元 里実, 高井 寛子, 渡邊 悠子, 岡田 知佳, 森 珠里, 石崎 邦子, 松本 久美, 岡 美穂, 黒川 恵理, 吉田 栄人, 金田 安史, 大原 直也, 内藤 真理子, 山田 毅, 松本 壮吉, Reed Steven, Skeiky Yasir, Gillis Steven

    結核   78 ( 3 )   278 - 278   2003.3

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  • Novel DNA and recombinant BCG vaccinations against tuberculosis by the augmentation of cytotoxic activity

    M Okada, S Yoshida, N Ohara, T Yamada, Y Kaneda, T Tanaka, Y Kita, S Kuwayama, Y Muraki, Y Inanaga, N Kanamaru, Y Inoue, M Matsumoto, K Kimura, M Sakatani, T Mori

    FASEB JOURNAL   16 ( 4 )   A308 - A309   2002.3

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  • 細胞内寄生菌に対する感染防御免疫 抗酸菌感染に対する宿主防御と病変形成機序

    松本 壮吉, 小林 和夫

    日本細菌学雑誌   57 ( 1 )   69 - 69   2002.2

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  • ヒトマラリアの防御抗原を発現する組換えBCGワクチンの作製

    雪竹 英治, 大原 直也, 神原 廣二, 山田 毅, 松本 壮吉

    日本細菌学雑誌   56 ( 1 )   316 - 316   2001.2

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  • 抗酸菌抗原DNAワクチンとrBCGワクチンのモルモット免疫応答及び結核防御効果

    山本 三郎, 野島 康弘, 梅森 清子, 野間口 博子, 大原 直也, 山田 毅, 山本 十糸子, 佐藤 由紀夫, 松本 壮吉, 松尾 和浩

    日本細菌学雑誌   56 ( 1 )   315 - 315   2001.2

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  • A Toll-like receptor recognizes bacterial DNA (vol 408, pg 740, 2000)

    H Hemmi, O Takeuchi, T Kawai, T Kaisho, S Sato, H Sanjo, M Matsumoto, K Hoshino, H Wagner, K Takeda, S Akira

    NATURE   409 ( 6820 )   646 - U22   2001.2

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  • O157感染症予防のためのベロ毒素Bサブユニット分泌型組み換えBCGワクチンの開発

    藤井 潤, 内藤 真理子, 湯通堂 隆, 松本 壮吉, 山田 毅

    産業医科大学雑誌   22 ( 1 )   80 - 80   2000.3

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    Other Link： http://search.jamas.or.jp/link/ui/2000140881

  • 多剤耐性結核感染の対策とワクチン開発

    山田 毅, 松本 壮吉

    感染症学雑誌   74 ( 3 )   292 - 293   2000.3

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  • 耐性菌感染症の現状と対策 多剤耐性結核感染の対策とワクチン開発

    山田 毅, 松本 壮吉

    日本化学療法学会雑誌   48 ( 2 )   141 - 142   2000.2

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  • BCG及び組み換えBCGによるPlasmodium yoelii感染防御機構について

    松本 壮吉, 雪竹 英治, 神原 廣二, 山田 毅

    日本細菌学雑誌   54 ( 1 )   300 - 300   1999.2

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  • 抗酸菌の核酸結合性蛋白質(MDP1;mycobacterial DNA binding protein 1)の同定と解析

    松本 壮吉, 雪竹 英治, 松尾 長光, 山田 毅

    日本細菌学雑誌   54 ( 1 )   188 - 188   1999.2

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  • 顎関節症患者の関節滑液中の抗体が認識する抗酸菌の44kDa蛋白質について

    安達 紀子, 松本 壮吉, 松尾 長光, 大原 直也, 内藤 真理子, 雪竹 英治, 山田 毅

    日本細菌学雑誌   54 ( 1 )   312 - 312   1999.2

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  • ゲノム情報 結核菌の全ゲノム配列決定の意義

    山田 毅, 松本 壮吉, 山田 博

    蛋白質・核酸・酵素   44 ( 1 )   65 - 70   1999.1

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    Other Link： http://search.jamas.or.jp/link/ui/1999089017

  • Identification of a novel DNA-binding protein from Mycobacterium bovis bacillus Calmette-Guerin

    S Matsumoto, H Yukitake, M Furugen, T Matsuo, T Mineta, T Yamada

    MICROBIOLOGY AND IMMUNOLOGY   43 ( 11 )   1027 - 1036   1999

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  • マラリア原虫の防御免疫にかかわる研究

    神原 廣二, 上村 春樹, 柳 哲雄, 中澤 秀介, 坪井 敬文, 大橋 真, 前野 芳正, 楠原 康弘, 山田 毅, 松本 壮吉

    長崎大学熱帯医学研究所共同研究報告集   11   18 - 22   1999

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  • Biological significance of the complete sequencing of Mycobacterium tuberculosis

    T. Yamada, S. Matsumoto, H. Yamada

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   44 ( 1 )   65 - 70   1999

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  • Identification of a protein possessing slow growth-generating activity from Mycobacterium bovis bacillus Calmette-Guerin (BCG)

    MATSUMOTO Sohkichi, YUKITAKE Hideharu, MATSUO Takemitsu, MINEDA Takao, YAMADA Takeshi

    21   502 - 502   1998.12

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  • The binding mechanism between fibronectin and the mycobacterial immunodominant antigen, α antigen

    NAITO M., OHARA N., MATSUMOTO S., YAMADA T.

    21   314 - 314   1998.12

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  • Recombinant Mycobacterium bovis Bacillus Calmette-Guerin secreting merozoite surface protein 1 (MSP1) induces protection against rodent malaria parasite infection depending on MSP1-stimulated interferon gamma and parasite-specific antibodies

    S Matsumoto, H Yukitake, H Kanbara, T Yamada

    JOURNAL OF EXPERIMENTAL MEDICINE   188 ( 5 )   845 - 854   1998.9

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  • マウスIL-2分泌recombinant BCGの作成及びその活性について 膀胱癌細胞に対する抗腫瘍エフェクターの解析

    山田 博, 松本 壮吉, 松本 哲朗, 山田 毅, 山下 優毅

    西日本泌尿器科   60 ( 増刊 )   146 - 146   1998.9

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  • 細菌の遅発育性を誘導する,抗酸菌由来,新規蛋白質の同定

    松本 壮吉, 峰田 天雄, 山田 毅

    歯科基礎医学会雑誌   40 ( 抄録 )   361 - 361   1998.9

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  • Immunological characterization of alpha antigen of Mycobacterium kansasii: B-cell epitope mapping

    M Naito, N Ohara, S Matsumoto, T Yamada

    SCANDINAVIAN JOURNAL OF IMMUNOLOGY   48 ( 1 )   73 - 78   1998.7

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  • The 16-kDa alpha-crystallin-like protein of Mycobacterium bovis BCG is produced under conditions of oxygen deficiency and is associated with ribosomes

    Y Tabira, N Ohara, N Ohara, H Kitaura, S Matsumoto, M Naito, T Yamada

    RESEARCH IN MICROBIOLOGY   149 ( 4 )   255 - 264   1998.4

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  • Putative heat shock protein 70 gene from Actinobacillus actinomycetemcomitans: molecular cloning and sequence analysis of its gene

    J Minami, S Matsumoto, T Yamada

    ORAL MICROBIOLOGY AND IMMUNOLOGY   13 ( 2 )   113 - 119   1998.4

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  • ハンセン氏病予防ワクチンの開発

    山田 毅, 内藤 真理子, 大原 直也, 松本 壮吉, 松岡 正典, 野間口 博子

    日本ハンセン病学会雑誌   67 ( 1 )   63 - 63   1998.3

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  • 組み換えBCGにより誘導される,マラリア原虫感染防御免疫の解析

    松本 壮吉

    日本細菌学雑誌   53 ( 1 )   237 - 237   1998.2

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  • The novel fibronectin-binding motif and key residues of mycobacteria

    M Naito, N Ohara, S Matsumoto, T Yamada

    JOURNAL OF BIOLOGICAL CHEMISTRY   273 ( 5 )   2905 - 2909   1998.1

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  • Shotgun cloning and characterization of the thymidylate synthase-encoding gene from Mycobacterium bovis BCG

    S Matsumoto, H Yukitake, N Ohara, T Dairi, H Kanbara, T Yamada

    MICROBIOLOGY AND IMMUNOLOGY   42 ( 1 )   15 - 21   1998

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  • Internalization of Mycobacterium bovis bacillus Calmette-Gv(]J1117[)rin into osteoblast-like MC3T3-E1 Cell and bone resorptive responses of the cells against the infection(共著)

    Scandinavian Journal of Immunology   47   453 - 458   1998

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  • HrpA, a new ribosome-associated protein which appears in heat-stressed Mycobacterium bovis Bacillus Calmette-Guerin

    N Ohara, N Ohara, M Naito, C Miyazaki, S Matsumoto, Y Tabira, T Yamada

    JOURNAL OF BACTERIOLOGY   179 ( 20 )   6495 - 6498   1997.10

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  • Analysis of the genes encoding the antigen 85 complex and MPT51 from Mycobacterium avium

    N Ohara, N OharaWada, H Kitaura, T Nishiyama, S Matsumoto, T Yamada

    INFECTION AND IMMUNITY   65 ( 9 )   3680 - 3685   1997.9

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  • 顎関節症患者の関節滑液中の抗体が認識する,抗酸菌の蛋白質抗原の同定

    松本 壮吉

    歯科基礎医学会雑誌   39 ( 抄録 )   462 - 462   1997.9

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  • Species-specific B-cell epitope on the C-terminal region of the alpha antigen from Mycobacterium scrofulaceum

    M Takano, N Ohara, M Naito, S Matsumoto, T Matsuo, R Shirai, A Mizuno, T Yamada

    MICROBIAL PATHOGENESIS   23 ( 2 )   95 - 100   1997.8

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  • Inhibition of multiplication of Mycobacterium leprae in mouse foot pads by immunization with ribosomal fraction and culture filtrate from Mycobacterium bovis BCG

    M Matsuoka, H Nomaguchi, H Yukitake, N Ohara, S Matsumoto, K Mise, T Yamada

    VACCINE   15 ( 11 )   1214 - 1217   1997.8

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  • Transcriptional analysis of the groESL operon from Porphyromonas gingivalis. International journal

    H Hotokezaka, N Ohara, H Hayashida, S Matsumoto, T Matsuo, M Naito, K Kobayashi, T Yamada

    Oral microbiology and immunology   12 ( 4 )   236 - 9   1997.8

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    Transcriptional analysis of the groESL operon from Porphyromonas gingivalis, one of the obligative anaerobic oral microorganisms implicated in adult periodontitis, was performed. P. gingivalis 381 cultured at 37 degrees C was shifted to 42 degrees C, 45 degrees C or 48 degrees C for 10 mins. Northern hybridization analysis revealed that a band with 2.1-kb (kilo base pair) was observed, and the transcripts increased greatly by heat shock. Primer extension and S1 mapping detected four different 5'-ending sites of the mRNAs at the upstream region of the groES. Three sites out of the four were heat-inducible. There were inverted repeats and a Escherichia coli sigma 32-recognizing consensus sequence in the promoter region of the groESL, which may be relevant to the regulation of transcription of groESL operon in P. gingivalis. Both a heat shock promoter and inverted repeats may be relevant to the transcriptional regulation of the groESL operon in P. gingivalis.

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  • BCGを用いた,マラリアワクチンの開発

    松本 壮吉

    Parasitology International   46 ( Suppl. )   61 - 61   1997.4

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  • 顎関節症患者の関節滑液に認められるマイコバクテリアの43kDa蛋白質に対する抗体について

    松本 壮吉

    日本細菌学雑誌   52 ( 1 )   186 - 186   1997.1

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  • Mycobacterium bovis BCG由来のチミジル酸シンターゼについて

    松本 壮吉

    日本細菌学雑誌   52 ( 1 )   186 - 186   1997.1

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  • 組み換えBCGワクチンシステムを用いた,マラリアワクチンの開発

    松本 壮吉

    日本細菌学雑誌   52 ( 1 )   332 - 332   1997.1

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  • BCG菌の赤内型マラリア原虫に対する感染予防効果について

    松本 壮吉

    日本細菌学雑誌   52 ( 1 )   309 - 309   1997.1

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  • 顎関節症患者の関節液中に認められる抗mycobacteria抗体について

    松本 壮吉

    歯科基礎医学会雑誌   38 ( 抄録 )   498 - 498   1996.8

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  • Cloning and sequencing of an MPB70 homologue corresponding to MPB83 from Mycobacterium bovis BCG

    T Matsuo, H Matsuo, N Ohara, S Matsumoto, H Kitaura, A Mizuno, T Yamada

    SCANDINAVIAN JOURNAL OF IMMUNOLOGY   43 ( 5 )   483 - 489   1996.5

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  • Essential role of Stat6 in IL-4 signalling

    K Takeda, T Tanaka, W Shi, M Matsumoto, M Minami, S Kashiwamura, K Nakanishi, N Yoshida, T Kishimoto, S Akira

    NATURE   380 ( 6575 )   627 - 630   1996.4

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  • 組み換えBCGを用いたマラリアワクチンの開発

    松本 壮吉

    寄生虫学雑誌   45 ( Suppl. )   34 - 34   1996.3

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  • Long-lasting immune response induced by recombinant Bacillus Calmette-Guerin (BCG) secretion system

    N Wada, N Ohara, M Kameoka, Y Nishino, S Matsumoto, T Nishiyama, M Naito, H Yukitake, Y Okada, K Ikuta, T Yamada

    SCANDINAVIAN JOURNAL OF IMMUNOLOGY   43 ( 2 )   202 - 209   1996.2

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  • A stable Escherichia coli mycobacteria shuttle vector 'pSO246' in Mycobacterium bovis BCG

    S Matsumoto, M Tamaki, H Yukitake, T Matsuo, M Naito, H Teraoka, T Yamada

    FEMS MICROBIOLOGY LETTERS   135 ( 2-3 )   237 - 243   1996.1

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  • Stable expression and secretion of the B-cell epitope of rodent malaria from Mycobacterium bovis BCG and induction of long-lasting humoral response in mouse

    S Matsumoto, T Yanagi, N Ohara, N Wada, H Kanbara, T Yamada

    VACCINE   14 ( 1 )   54 - 60   1996.1

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  • 組み換えBCGワクチンシステムを用いた,マラリアワクチンの開発

    松本 壮吉

    日本細菌学雑誌   51 ( 1 )   238 - 238   1996.1

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  • E Long-lasting immune response induced by recombinant Bacillus Calmette-Guerin (BCG) secretion system.

    Wada N., Ohara N., Kameoka M., Nishino Y., Matsumoto S., Nishiyama T., Naito M., Yukitake H., Okada Y., Ikuta K., Yamada T.

    Collected papers from the Institute of Immunological Science Hokkaido University   19   26 - 33   1996

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    Language：English   Publisher：北海道大学  

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  • ヒト結核の感染・発病と免疫 結核発病における菌側の因子:抗酸菌の抗原の研究の意味

    山田 毅, 大原 直也, 松本 壮吉

    結核   70 ( 11 )   639 - 644   1995.11

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  • 結核菌群特異的抗原MPB70の研究

    松本 壮吉

    歯科基礎医学会雑誌   37 ( 抄録 )   144 - 144   1995.8

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  • DIFFERENTIAL TRANSCRIPTION OF THE MPB70 GENES IN 2 MAJOR GROUPS OF MYCOBACTERIUM-BOVIS BCG SUBSTRAINS

    T MATSUO, S MATSUMOTO, N OHARA, H KITAURA, A MIZUNO, T YAMADA

    MICROBIOLOGY-UK   141   1601 - 1607   1995.7

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  • Characterization of the gene encoding the MPB51, one of the major secreted protein antigens of Mycobacterium bovis BCG, and identification of the secreted protein closely related to the fibronectin binding 85 complex. International journal

    N Ohara, H Kitaura, H Hotokezaka, T Nishiyama, N Wada, S Matsumoto, T Matsuo, M Naito, T Yamada

    Scandinavian journal of immunology   41 ( 5 )   433 - 42   1995.5

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    The secreted protein MPB51 is one of the major proteins in the culture filtrate of Mycobacterium bovis BCG (BCG) and is a protein immunologically cross-reacting with the fibronectin binding 85 complex secreted by this bacterium. The gene encoding MPB51 (mpb51) was cloned, sequenced, and expressed in Escherichia coli. The mpb51 gene was mapped downstream of the gene for 85A component with 179 bp spaces. The mpb51 gene encoded 299 amino acids, including 33 amino acids for the signal peptide, followed by 266 amino acids for the mature protein with a molecular mass of 27807.37 Da. This is the first complete sequence of MPB51. MPB51 showed 37-43% homology to the components of 85 complex. Two-dimensional electrophoresis of culture fluids of BCG and Western blotting indicated the existence of the other novel protein(s) which strongly cross-reacted with the alpha antigen (85B) and MPB51.

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  • Cloning and sequencing of a unique antigen MPT70 from Mycobacterium tuberculosis H37Rv and expression in BCG using E. coli-mycobacteria shuttle vector. International journal

    S Matsumoto, T Matsuo, N Ohara, H Hotokezaka, M Naito, J Minami, T Yamada

    Scandinavian journal of immunology   41 ( 3 )   281 - 7   1995.3

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    MPB70 is known to be an immunogenic mycobacterial protein secreted in large amounts from Mycobacterium bovis BCG (BCG) Tokyo. The analogous gene for MPT70 was cloned from Mycobacterium tuberculosis H37Rv which produces this protein in only a small amount. The gene encoding 193 amino acid residues including 30 amino acids for the signal peptide, the promoter-like sequence, and the ribosome-binding site, was completely identical to that of BCG Tokyo. Computer analysis revealed that the carboxy-terminal half of MPT70 was homologous to amino acid sequences of fasciclin I, osteoblast-specific factor 2 (OSF-2), and human transforming growth factor-beta induced gene product (beta IG-H3). Escherichia coli (E. coli) -mycobacteria shuttle vectors containing mpt70 or mpb70 genes 0.7kbp upstream of the 5' end of them were able to be expressed in BCG Pasteur which is a MPB70 low-producer, but the extent of the expression was not that of a high-producer.

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  • 結核菌由来抗原性蛋白質MPT70の遺伝子及びその発現解析

    松本 壮吉

    日本細菌学雑誌   50 ( 1 )   210 - 210   1995.1

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  • 1. The role of some cellular components of bacterial parasites in determining the incidence of tuberculosis: Studies on mycobacterial antigens, with special reference to mycobacterial immunoreactive ribosomal and secreted proteins

    T. Yamada, N. Ohara, S. Matsumoto, T. Matsuo, H. Kitaura, H. Yukitake, N. Wada, T. Nishiyama, M. Naito, M. Kinomoto, M. Kimura

    Kekkaku   70 ( 11 )   639 - 644   1995

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  • Biochemical and immunological characterization of ribosomal fraction and culture filtrate from ┣DBmycobacterium(/)-┫DB

    Takeshi Yamada, Naoya Ohara, Naoko Wada, Sokichi Matsumoto, Hideharu Yukitake, Takemitsu Matsuo, Hideki Kitamura, Mikiko Takano, Takeshi Nishiyama, Hiroko Nomoguchi, Masanori Matsuo

    Actinomycetology   9 ( 2 )   228 - 235   1995

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    Language：English   Publisher：The Society for Actinomycetes Japan  

    DOI： 10.3209/saj.9_228

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    Other Link： http://search.jamas.or.jp/link/ui/1996082802

  • マラリアB-cellエピトープ発現系の研究

    松本 壮吉

    日本細菌学雑誌   49 ( 3〜4 )   507 - 507   1994.5

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  • マラリアスポロゾイトワクチンの開発

    松本 壮吉

    日本細菌学雑誌   49 ( 1 )   276 - 276   1994.1

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  • "N-ACETYLNEURAMINYLLACTOSYLCERAMIDE, GM3-NEUAC, A NEW INFLUENZA-A VIRUS RECEPTOR WHICH MEDIATES THE ADSORPTION-FUSION PROCESS OF VIRAL-INFECTION - BINDING-SPECIFICITY OF INFLUENZA-VIRUS A/AICHI/2/68 (H3N2) TO MEMBRANE-ASSOCIATED GM3 WITH DIFFERENT MOLECULAR-SPECIES OF SIALIC-ACID

    Y SUZUKI, M MATSUNAGA, M MATSUMOTO

    JOURNAL OF BIOLOGICAL CHEMISTRY   260 ( 3 )   1362 - 1365   1985

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Presentations

  • Biofilms and dormancy that related to intractable infectious diseases caused by mycobacteria Invited

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    Event date： 2025.5

    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • Intrinsically disordered histone-like protein that induces mycobacterial dormancy Invited

    Akihito Nishiyama, Masahiro Shimizu, Noriyuki Kodera, Anna Savitskaya, Yuriko Ozeki, Kouta Mayanagi, Takehiro Yamaguchi, Amina Kaboso Shaban, Yoshitaka Tateishi, Sohkichi Matsumoto

    日米医学協力計画60周年記念・第25回EID会議 

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    Event date： 2025.3

    Language：English   Presentation type：Oral presentation (keynote)  

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  • Tackling Tuberculosis: Toward Elucidating Dormancy Mechanism and Detecting Disease Onset Invited

    Sohkichi Matsumoto

    Bridging Science and Global Health Challenges in Tuberculosis 

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    Event date： 2024.12

    Language：English   Presentation type：Oral presentation (invited, special)  

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  • 抗酸菌研究の最前線 Invited

    松本 壮吉

    第94回日本感染症学会 

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    Event date： 2024.11

    Language：Japanese   Presentation type：Oral presentation (invited, special)  

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  • 結核を対策するために；休眠現象の解明や結核発症の検出にむけて Invited

    松本 壮吉

    第97回日本生化学会大会 

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    Event date： 2024.11

    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • Basic Knowledge and Techniques for Drug Development Against Tuberculosis Invited

    Sohkichi Matsumoto

    International Conference of Herbal Medicine 2024 

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    Event date： 2024.7

    Language：English   Presentation type：Oral presentation (keynote)  

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  • 薬剤抵抗性を生む、天然変性ヒストン様蛋白質による、抗酸菌の休眠現象 Invited

    松本 壮吉

    第98回日本感染症学会総会・学術講演会・第72回日本化学療法学会総会 

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    Event date： 2024.6

    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • 抗酸菌の天然変性ヒストン様蛋白質－その機能と休眠菌形成における役割 Invited

    西山 晃史, 清水 将裕, 古寺 哲幸, 尾関 百合子, 真柳 浩太, 山口 雄大, 立石 善隆, 吉田 豊, 松本 壮吉

    第99回 日本結核・非結核性抗酸菌症学会学術講演会 

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    Event date： 2024.5 - 2024.6

    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • Basic Knowledge for the development of drugs against tuberculosis Invited

    Sohkichi Matsumoto

    The 13th ISISM, the 10th ISIBio, the 20th ACM 2023 and Special Symposium for Drug Discovery supported by SATREPS ADD Project 

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    Event date： 2023.11

    Language：English   Presentation type：Symposium, workshop panel (nominated)  

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  • 抗酸菌のヒストン様蛋白質による天然変性領域に依存的な休眠誘導 Invited

    松本 壮吉

    第96回日本生化学会大会 

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    Event date： 2023.10

    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • Immune responses to Mycobacterium tuberculosis proteins and their application to TB diagnosis and vaccine development Invited

    Sohkichi Matsumoto

    2nd INTERNATIONAL CONFERENCE ON INFECTIOUS AND TROPICAL DISEASES (ICITD) IN CONJUNCTION WITH CLINICAL MICROBIOLOGY CONTINUING MEDICAL EDUCATION (CM-CME) 

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    Event date： 2023.10

    Language：English   Presentation type：Oral presentation (keynote)  

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  • 結核や非結核性抗酸菌症 Invited

    松本 壮吉

    地研支部微生物研究部会研修会 

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    Event date： 2023.10

    Language：Japanese   Presentation type：Oral presentation (invited, special)  

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  • 人の長寿と長生きの抗酸菌；抗酸菌がゆっくりと生きて頻繁に眠るしくみから、対策技術開発への展開可能性 Invited

    松本 壮吉

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    Event date： 2023.5

    Language：Japanese   Presentation type：Oral presentation (invited, special)  

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  • 抗酸菌症とワクチン Invited

    松本 壮吉

    第97回結核・非結核性抗酸菌症学会総会 

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    Event date： 2023.5

    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • Current update on drug susceptibility test (DST) for tuberculosis Invited

    Sohkichi Matsumoto

    Perhimpunan Dokter Spesialis Mikrobiology Klink Indonesia 

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    Event date： 2022.3

    Presentation type：Oral presentation (invited, special)  

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  • Development of control strategies against tuberculosis based on molecular mechanisms of persistence of tuberculosis and host immune response to it (Abstract book P8). Invited

    Sohkichi Matsumoto

    10th National Congress of Indonesian Society for Clinical Microbiology (KONAS-PAMKI) 

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    Event date： 2021.9

    Language：English   Presentation type：Oral presentation (invited, special)  

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  • The molecular and structural mechanisms of inactivation of DNA function in mycobacterial dormant persisters Invited

    Sohkichi Matsumoto, Akihito Nishiyama

    The 19th Awaji International Forum on Infection and Immunity | Bacteriology. Symposium 

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    Event date： 2021.9

    Language：English   Presentation type：Symposium, workshop panel (nominated)  

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  • BCGと新型コロナウイルス感染症（COVID-19） Invited

    松本 壮吉

    第96回結核・非結核性抗酸菌症学会総会 

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    Event date： 2021.6

    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • 組換えBCGを用いた、難病に対する多価ワクチンの開発 Invited

    松本 壮吉

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    Event date： 2021.3

    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • 結核：歴史と現状および対策 Invited

    松本 壮吉

    第451回ICD講習会  2024.7 

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  • 結核とBCG Invited

    松本 壮吉

    AMED SCARDセミナー  2023.12 

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    Language：Japanese   Presentation type：Oral presentation (invited, special)  

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  • 結核と抗酸菌症；眠る巨人のメカニズム Invited

    松本 壮吉

    Advanced Seminar Series；大阪大学微生物病研究所  2023.7 

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    Language：Japanese   Presentation type：Oral presentation (invited, special)  

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  • Longevity of human being and long living mycobacteria Invited

    Sohkichi Matsumoto

    AFCM Seminar, Cairo, Egypt  2023.6 

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  • 結核ワクチンについて Invited

    松本 壮吉

    第98回日本結核・非結核性抗酸菌症学会ランチョンセミナー  2023.6 

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    Language：Japanese   Presentation type：Oral presentation (invited, special)  

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  • 結核；潜伏維持か発症か？―病勢を左右する菌と宿主の因子についての最近の知見 Invited

    松本 壮吉

    2020.2 

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    Presentation type：Symposium, workshop panel (nominated)  

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  • 私はこうしてPIになれたんだとおもいます Invited

    松本 壮吉

    第93回日本細菌学会総会  2020.2 

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  • 結核の潜在化のメカニズムとIGRAなとの結核菌感染診断について Invited

    松本 壮吉

    第132回日本結核病学会東海地方会  2018.11 

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    Language：Japanese   Presentation type：Oral presentation (invited, special)  

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  • Development of control strategies against tuberculosis based on molecular mechanisms of persistence of tuberculosis and host immune response to it (Abstract book P8). Invited International conference

    MATSUMOTO Sohkichi

    The 1st International Scientific Meeting on Clinical Microbiology and Infectious Diseases (ISM-CMID). 10th National Congress of Indonesian Society for Clinical Microbiology (KONAS-PAMKI), 12th National Symposium-Indonesian Antimicrobial Resistance Watch (  2018.10 

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    Language：English   Presentation type：Symposium, workshop panel (nominated)  

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  • From biology of Mycobacterium to the development of the control strategies against tuberculosis, Invited International conference

    MATSUMOTO Sohkichi

    The 13th Nagasaki-Singapore Medical Symposium  2017.5 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • 抗酸菌の「長生き」のメカニズムと結核対策への応用

    松本 壮吉

    第92回日本結核病学会総会  2017.3 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • Diagnosis of TB infections. Invited International conference

    MATSUMOTO Sohkichi

    6th Conference of International Union Against Tuberculosis and Lung Disease, Asia Pacific Region  2017.3 

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  • 結核・抗酸菌に特徴的な薬剤標的と新規薬剤の開発研究 Invited

    松本 壮吉

    65回日本感染症学会東日本地方会  2016.10 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • Tuberculosis; Facts, Mechanisms, and Research to control it. Invited International conference

    MATSUMOTO Sohkichi

    Japan-Russia G-MedEx Project: International symposium of educational and scientific development-2016.  2016.9 

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    Language：English   Presentation type：Symposium, workshop panel (nominated)  

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  • 結核・抗酸菌の潜伏感染メカニズム

    松本 壮吉

    第89回日本細菌学会総会  2016.3 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • Analysis of asympotomatic tuberculosis and its risks, Invited International conference

    MATSUMOTO Sohkichi

    50th anniversary, US-Japan, Cooperative Medical Science Program,  2016.1 

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    Language：English   Presentation type：Symposium, workshop panel (nominated)  

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  • 結核の歴史や現状と、潜在性結核に学ぶ新しい結核制御法開発の試み Invited

    松本 壮吉

    第56回日本熱帯医学会大会  2015.12 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • 結核・抗酸菌の遅発育性や休眠現象と新しい抗酸菌症戦略の可能性 Invited

    松本 壮吉

    第3回 福岡マイコバクテリオーシスシンポジウム  2015.10 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • 人をすみかとする結核菌と結核—病原体の誕生から広がりと現状 Invited

    松本 壮吉

    平成27年度にいがた市民大学  2015.6 

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    Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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  • 結核菌の増殖制御や潜在性結核の解析および、結核ワクチンの開発研究

    松本 壮吉

    第90回結核病学会  2015.3 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • 結核菌の増殖制御や潜在性結核の解析および、結核ワクチンの開発研究 Invited

    松本 壮吉

    第22回呼吸器疾患・感染症研究会  2014.8 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • A Novel mechanism of growth phase dependent INH-resistance in mycobacteria, Invited International conference

    MATSUMOTO Sohkichi

    16th International Conference on Emerging Infectious Diseases in the Pacific Rim,  2014.2 

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  • 抗酸菌の潜伏感染や薬剤抵抗性に関わる分子メカニズム Invited

    松本 壮吉

    第86回日本ハンセン病学会総会・学術大会  2013.5 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • 結核菌の潜伏感染機構と新しい結核制御の可能性 Invited

    松本 壮吉

    第87回日本細菌学会総会  2013.3 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • Functions of mycobacterial DNA binding protein 1 (MDP1) and its contribution to the persistent infection of Mycobacterium tuberculosis, Invited International conference

    MATSUMOTO Sohkichi

    The 11th International Symposium on Microbiology  2012.9 

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  • 結核菌の増殖、長期生存、および静止期以降の薬剤抵抗性獲得の分子メカニズム Invited

    松本 壮吉

    第26回Bacterial Adherence and Biofilm学術集会  2012.7 

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  • 結核菌の休眠現象と潜在性結核診断の可能性

    松本 壮吉

    特定非営利活動法人結核診断研究会・第一回総会  2012.5 

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  • 結核菌がゆっくりと長く生きる機構と潜在性結核 Invited

    松本 壮吉

    第21回学会賞受賞者特別講演会  2012.1 

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  • Overview, Growth coordination of mycobacteria and latent Mycobacterium tuberculosis infection. Invited International conference

    MATSUMOTO Sohkichi

    6th US-Japan, Cooperative Medical Science Program,  2011.12 

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  • 先端医科学研究の現状。結核菌の増殖制御機構と結核制圧戦略 Invited

    松本 壮吉

    第7回霊長類医科学フォーラム  2011.11 

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  • 熱帯医学からの発信。結核菌がゆっくりと長く生きるメカニズムと結核の制圧を目指した研究。 Invited

    松本 壮吉

    第52回日本熱帯医学会大会 第26回日本国際保健医療学会学術大会 合同大会  2011.11 

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  • 再考VNC(Viable but Non-Culturable cells)！細菌に学ぶ生残戦略。結核菌の休眠現象と潜在性結核

    松本 壮吉

    第84回日本生化学会  2011.9 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • Host Factors having an impact on the growth of Mycobacterium tuberculosis. Invited International conference

    MATSUMOTO Sohkichi

    International Union of Microbiological Societies 2011 Congress  2011.9 

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    Language：English   Presentation type：Symposium, workshop panel (nominated)  

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  • 結核研究の最先端。潜在性結核の分子機構と結核制圧研究 Invited

    松本 壮吉

    第28回日本医学会総会2011  2011.4 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • 結核菌の長生きのメカニズムと潜在性結核 Invited

    松本 壮吉

    第5回久留米日和見感染症研究会学術講演会  2011.2 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • 結核菌の気道ヒアルロン酸を利用した感染と生体内増殖 Invited

    松本 壮吉

    第22回微生物シンポジウム  2010.9 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • Mycobacteria exploit host hyaluronan for efficient extracellular replication, Invited International conference

    MATSUMOTO Sohkichi

    The 8th international conference of hyaluronan  2010.6 

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    Language：English   Presentation type：Symposium, workshop panel (nominated)  

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  • 結核菌の長生きのメカニズム；休眠現象と潜在性結核 Invited

    松本 壮吉

    第27回東海薬物治療研究会  2010.5 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • 抗酸菌感染症における感染制御の進歩 Invited

    松本 壮吉

    第84回日本感染症学会総会  2010.4 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • Molecular mechanisms of latent tuberculosis infection (LTBI) and development of diagnosis of LTBI, Invited International conference

    MATSUMOTO Sohkichi

    2010.3 

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    Language：English   Presentation type：Symposium, workshop panel (nominated)  

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  • 気道ヒアルロン酸を利用した、結核菌の感染と増殖のストラテジー

    松本 壮吉

    第50回日本熱帯医学会  2009.10 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • From the function of a protein to molecular pathogenesis of mycobacteria Invited

    MATSUMOTO Sohkichi

    2009.3 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • 結核菌病原因子による病変形成と感染防御 Invited

    松本 壮吉

    第82回日本結核病学会総会  2007.6 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • 結核菌潜伏感染の分子機構と新規治療戦略 Invited

    松本 壮吉

    第79回日本結核病学会  2004.4 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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▶ display all

Industrial property rights

  • 免疫原性を有するMDP1の製造方法

    松本 壮吉

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    Application no：特願2018-107292  Date applied：2018.6

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  • MDP1を用いた炭水化物を有する物質の分離方法

    松本 壮吉

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    Application no：特願2008-277012  Date applied：2008.10

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  • MDP1による微生物を凝集および／または沈殿させる方法

    松本 壮吉

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    Application no：特願PCT/JP2009/061819 

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Awards

  • 小林六造記念賞

    2011   日本細菌学会   結核菌の病原性および増殖制御機構の分子遺伝学的解析と応用研究

    松本 壮吉

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Research Projects

  • 結核・抗酸菌症の治療期間を短縮し、疾病母体を除する革新的薬剤開発に向けた基盤研究

    Grant number：24K02277

    2024.4 - 2028.3

    System name：科学研究費助成事業

    Research category：基盤研究(B)

    Awarding organization：日本学術振興会

    松本 壮吉, 清水 将裕, 伊東 孝祐, 古寺 哲幸

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    Grant amount：\18720000 （ Direct Cost: \14400000 、 Indirect Cost：\4320000 ）

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  • International joint research aimed at developing new diagnostic and control methods for tuberculosis

    Grant number：21KK0136

    2021.10 - 2025.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

    Awarding organization：Japan Society for the Promotion of Science

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    Grant amount：\19240000 （ Direct Cost: \14800000 、 Indirect Cost：\4440000 ）

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  • 天然変性ヒストン様蛋白質による、結核菌の個性の創出と多様性獲得の分子機構

    Grant number：20H03483

    2020.4 - 2024.3

    System name：科学研究費助成事業

    Research category：基盤研究(B)

    Awarding organization：日本学術振興会

    松本 壮吉, 白井 剛, 伊東 孝祐, 真柳 浩太

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    Grant amount：\17680000 （ Direct Cost: \13600000 、 Indirect Cost：\4080000 ）

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  • Analysis of molecular mechanism of mitochondrial damage and immune suppression induced by Mycobacterium tuberculosis

    Grant number：20H03487

    2020.4 - 2023.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

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    Grant amount：\17550000 （ Direct Cost: \13500000 、 Indirect Cost：\4050000 ）

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  • A new treatment for postoperative intractable inflammatory condition focusing on antibacterial effect and intestinal regulation of yogurt

    Grant number：16K21041

    2016.4 - 2019.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Young Scientists (B)

    Awarding organization：Japan Society for the Promotion of Science

    Tajima Yosuke, WAKAI Toshifumi, MATSUMOTO Sohkichi, TATEISHI Yoshitaka, KURAMOTO Miyako

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    Grant amount：\3900000 （ Direct Cost: \3000000 、 Indirect Cost：\900000 ）

    This research suggests that the antibacterial active ingredient of Yasuda yogurt against MRSA is lactic acid and hydrogen peroxide produced by lactic acid bacteria Lactobacillus delbrueckii subsp bulgaricus. Now we plan to examine the immunological effects of the infection and the therapeutic effect of Yasuda yogurt on ileal pouchitis after surgery for ulcerative colitis.

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  • Study of tuberculosis latency and development of anti-tuberculosis strategy by keeping latent state

    Grant number：16H05187

    2016.4 - 2019.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    Matsumoto Sohkichi, Mekura Ryoji, Ozeki Yuriko, Katahira Masato, Yamaguchi Takehiro

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    Grant amount：\17940000 （ Direct Cost: \13800000 、 Indirect Cost：\4140000 ）

    Tuberculosis is a serious health threat that kills more than 1.5 million people annually. Mycobacterium tuberculosis, an etiologic agent of tuberculosis, persistently infects one third of the human population, and 5 to 10% of them develops tuberculosis. Accordingly, prevention of the progression from latent tuberculosis is an efficient for tuberculosis control. At the latent stage M. tuberculosis is under dormant state where growth has ceased. Here we showed importance of suppression of energy production and fatty acid synthesis of mycobacteria for long term survival of mycobacterial after entering stationary phases. Our data provided reasonable basis of establishing a new control strategy against tuberculosis by deterring the disease onset.

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  • Study of the protective immune mechanism against tuberculosis through pDC activation induced by CpG-ODN and Mycobacterium tuberculosis antigen

    Grant number：15K09565

    2015.4 - 2018.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    Suzuki Fumiko, MATSUMOTO Sohkichi

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

    The major protein of Mycobacterium tuberculosis, “M”, is expressed both in the growth phase and in the resting phase. On the other hand, the palindromic deoxyoligonucleotide, “G”, containing a CpG motif induces the activation of plasmacytoid dendritic cells (pDCs). Human peripheral mononuclear cells co-cultured with a combination of “M” and “G” showed enhanced IFN-α production from the pDCs and upregulation of costimulators on the surface of dendritic cells (DCs). It is suggested that both increases in IFN-α production and costimulator expression are dependent on efficient transfer of “G” to DCs mediated by “M”.
    The synergistic immune mechanism induced by the combination of “M” antigen and “G” adjuvant is valuable as the scientific basis for the development of new vaccines against tuberculosis.

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  • Investigation of genomic characters specific for high-virulence multidrug-resistant Mycobacterium tuberculosis

    Grant number：15K08489

    2015.4 - 2018.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    Tamaru Aki

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

    We found a peculiar genotype, named V02, accounted for 12% of analyzed MDR-Mtb and consisted of only MDR-Mtb from genotyping analysis of Mycobacterium tuberculosis (Mtb). Since the genotype could be considered spreading MDR-Mtb in widely, we identified single nucleotide variants (SNVs) of 15 Mtb isolates belonging V02 genotype by genome wide mapping using Illumina-based short reads. By comparison between the 15 Mtb isolates and outgroup strains, 113 nonsynonymous SNVs were identified as specific to V02 isolates. Four genes with V02 specific SNPs concerned with the biological process of virulence of Mtb. Of 4 genes concerning with virulence, only pknI, reported to regulate the virulence of Mtb, Therefore, the mutation in pknI gene of Mtb belonging V02 genotype might contribute to the high spread of this genotype.

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  • The research in Kenya for the development a diagnostic method of asymptomatic M tuberculosis infection and disease progression

    Grant number：26305017

    2014.4 - 2018.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    Matsumoto Sohkichi, KANEKO Satoshi, FUJII Yoshito, OKA Mayuko, MAEKURA Ryoji, ICHINOSE Yoshio

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    Grant amount：\16250000 （ Direct Cost: \12500000 、 Indirect Cost：\3750000 ）

    This study was performed in tuberculosis-endemic area in Kenya to address molecular mechanisms of latency and know the fundamental knowledge for prediction of disease progression. We found some M. tuberculosis antigens are well recognized by host immune response, while some other antigens were done in individuals with asymptomatic infection. This suggested that detection of the immune responses to M. tuberculosis antigens can be applied for diagnosis of asymptomatic infection and disease progression.
    We also found elevated HDL-cholesterol levels in M. tuberculosis-infected individuals. We found human macrophages produces TNF-alpha, a host protective cytokine against tuberculosis, depending on TLR2 upon M. tuberculosis infection. And HDL suppresses TLR2 expression and its cellar signaling. These suggest that higher HDL level may be risk of both asymptomatic and active tuberculosis.

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  • Possibility of epigenetic regulation in bacteria through the post-translational modification of a histone-like protein

    Grant number：25670214

    2013.4 - 2016.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Challenging Exploratory Research

    Awarding organization：Japan Society for the Promotion of Science

    Matsumoto Sohkichi

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    Grant amount：\3900000 （ Direct Cost: \3000000 、 Indirect Cost：\900000 ）

    Post-translational modification of histones strongly affects chromatin functions and participates in the epigenetic regulation of the cell functions in eukaryotic cells. While bacteria produce the nucleoid-associated proteins, called histone-like proteins (HLP), but post-translational modification of HLP is hardly observed. Mycobacterium tuberculosis is a major human pathogen and kills over million people every year. This pathogen produces unique HLP, called MDP1 that is essential and controls expression of many sets of genes, and participates in regulation of mycobacterial growth and virulence. Interestingly post-translational modification occurs on MDP1, suggesting the possibility of post-translational modification-dependent control of MDP1 functions. In this research we analyzed the enzymes responsible for the modification of MDP1 in order to know the modification-dependent regulation of gene expression and epigenetic control in bacteria.

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  • Biofilm formation mechanism by intercellular signaling molecule of environmental pathogen

    Grant number：25350968

    2013.4 - 2016.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    Nishiuchi Yukiko, NISHIUCHI Yuji, MATSUMOTO Sohkichi

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    Grant amount：\4940000 （ Direct Cost: \3800000 、 Indirect Cost：\1140000 ）

    The incidence of pulmonary Mycobacterium avium complex (MAC) disease is increasing in Japan. This disease is generally developed by inhalation of MAC organisms occurring in the environment. MAC forms biofilm in the environment and hosts, and the biofilm can function to shelter MAC itself. Thus, the formed biofilm makes it difficult to eliminate MAC organisms from the infection sources and hosts. However, the biology and the regulatory mechanism of biofilm formation of MAC still remain unknown. The aim of this research is to elucidate these pending issues with the biofilm formation of MAC. We were able to demonstrate that the ambient hypoxia and eutrophic conditions promote MAC biofilm formation, and that glycolipids existing on the envelope of MAC, such as glycopeptidolipid, trehalose dimycolate, and trehalose monomycolate, are greatly involved in the formation of biofilm. Based on these findings, we are trying to find out measures that can effectively disinfect MAC organisms.

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  • The motion of novel strategy against tuberculosis based on the analysis of latent tuberculosis

    Grant number：24390106

    2012.4 - 2016.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    Matsumoto Sohkichi, ATo Manabu

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    Grant amount：\18460000 （ Direct Cost: \14200000 、 Indirect Cost：\4260000 ）

    One third world human population is latently infected with, a major human pathogen, Mycobacterium tuberculosis. The eradication of persisting M. tuberculosis has been thought to be the most successful action against tuberculosis, because M. tuberculosis generally has no environmental or animal reservoirs. Although M. tuberculosis is a well adapted intracellular pathogen, we believe that maintaining latent state can prevent the disease. In order to realize it, knowing molecular mechanisms of latency and disease development is important. In this research we established the mouse latency and reactivation model utilizing M. tuberculosis 18b, of which growth is dependent on the presence of streptomycin. And we showed that artificial gene expression causes growth arrest of Mycobacterium. This may provide reasonable accommodation to prevent the disease progression by downshifting the M. tuberculosis growth in vivo.

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  • Research for genetic specificity of the Multi Drug-resistant Mycobacterium tuberculosis Spreading in Osaka Prefecture.

    Grant number：24590651

    2012.4 - 2015.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    TAMARU Aki, MATSUMOTO Soukichi, WADA Takayuki

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    Grant amount：\5330000 （ Direct Cost: \4100000 、 Indirect Cost：\1230000 ）

    V02 strain: the spreading multi drug-resistant Mycobacterium tuberculosis stain in Osaka Prefecture, were subjected to genome-wide analysis by next-generation sequencing. Compared with H37Rv, 1,445 SNPs were common to all 15 isolates belonging to V02 strain. Although 51 SNPs were found among 15 isolates of V02 strain, and V02 strains were divided into two groups by two SNPs (A to C at 7582 and G to A at 3157508). These results shows the existence of V02 strains was not from one outbreak causing by one infectious source but the isolates of V02 may have common ancestor.

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  • Research in Kenya for the development of diagnosis of latent and active tuberculosis

    Grant number：23406011

    2011.4 - 2014.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    MATSUMOTO Sohkichi, HAMANO Shinjiro, KOBAYASHI Kazuo, ATO Manabu, SHIMADA Masaaki, KANEKO Satoshi

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    Grant amount：\18330000 （ Direct Cost: \14100000 、 Indirect Cost：\4230000 ）

    Tuberculosis is deadly infectious diseases found worldwide and remains a leading public health problem. The majority of TB cases arise from latent Mycobacterium tuberculosis infection (LTBI). However the risk of LTBI and development of TB from infection is largely unknown. We conducted comprehensive health survey in TB endemic area, Kenya Africa. In this study, 627 children from schools situated in two different sites, Mbita and Kwale districts, Kenya were enrolled. And we conducted comprehensive survey including biochemical analysis of blood and detection of infections of parasitic and bacterial pathogens. We found latent antigens M. tuberculosis is a candidates for more sensitive diagnosis of LTBI and hookworm infection is a risk of Mycobacterium tuberculosis infection besides active tuberculosis.

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  • Molecular mechanism of drug tolerance in dormant mycobacteria and identification of the drug target

    Grant number：21590486

    2009 - 2011

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    MATSUMOTO Sohkichi, NIKI Mamiko

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    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

    Tuberculosis is deadly infectious diseases found worldwide and remains a leading public health problem. Although isoniazid(INH) is a key drug for the treatment of tuberculosis(TB), tolerance against INH that causes prolonged treatment duration is a concern for effective TB chemotherapy. INH is a prodrug and is activated by the mycobacterial enzyme, KatG. We have shown that mycobacterial DNA-binding protein 1(MDP1), which is a histone-like protein conserved in mycobacteria, negatively regulates KatG transcription and leads to phenotypic tolerance to INH in mycobacteria. Mycobacterium smegmatis deficient for MDP1 exhibited increased expression of KatG and showed enhanced INH activation compared to the wild-type strain. Expression of MDP1 was increased in the stationary phase and conferred growth phase-dependent tolerance of M. smegmatis to INH. Regulation of KatG expression is conserved among M. smegmatis and Mycobacterium tuberculosis complex. Artificial reduction of MDP1 in Mycobacterium bovis BCG was shown to lead to increased KatG expression and susceptibility to INH. These data demonstrate the phenotypic tolerance mechanism to INH of mycobacteria by a histone-like protein.

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  • 潜在性結核対策を想定した、抗酸菌の長期生存を可能にする分子メカニズムの解明

    Grant number：21022043

    2009 - 2010

    System name：科学研究費助成事業

    Research category：特定領域研究

    Awarding organization：日本学術振興会

    松本 壮吉, 仁木 満美子, 岡 真優子

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    Grant amount：\7600000 （ Direct Cost: \7600000 ）

    抗酸菌感染症は現在も甚大な健康被害を及ぼしている。特に結核は年間180万人が死亡する最大級の細菌感染症である。結核菌は、人類の1/3に休眠状態で潜伏感染しており、感染者の10%において再燃が生じ病気が発症する。結核菌はヒト以外の宿主や自然環境下で生息できないため、潜伏感染菌の殺傷は病気の制圧に繋がるが、現在まで休眠機構は不明で潜伏感染菌を殺傷することができない。このような状況から抗酸菌の休眠機構を解明し対策を構築することは急務の課題であり本研究の目的である。
    本研究は、休眠期に制御される抗酸菌分子で休眠菌の長期生存を担う分子を同定し、各分子の機能を解析することで、休眠抗酸菌の生存維持のメカニズム解明に迫ることを目的とした。平成21年度には、休眠Mycobacterium smegmatisが発現する遺伝子群の同定を行った。その結果、M.smegmatis遺伝子のうち1200あまりは休眠期で発現が減少するが、逆に900あまりの遺伝子は増加することが判明した。また休眠の導入や維持に重要な役割を果たす蛋白質分子MDP1の欠失で休眠期に減少する遺伝子が約700、逆に増加するものが約500観察された。以上の結果から、M.smegmatis休眠菌は遺伝子の発現を継続していること、またMDP1が休眠期に発現する遺伝子の多くを制御していることが明らかとなった。22年度には、これらの遺伝子発現の変化が、MDP1のゲノムへの直接的結合に依存するのかを明らかにするため、MDP1が結合するゲノム領域をクロマチン沈降法によって沈降させ、その遺伝子配列を次世代シーケンサーで解析する、Chip-sequence法を実施した。現在、次世代シーケンサーによる大規模データを解析しており仮説を検証している。

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  • Ribosome-binding dependent induction of translational suppression and acquiring drug resistance caused by M. tuberculosis protein, MDP1

    Grant number：19590454

    2007 - 2008

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    0MATSUMOTO Sohkichi, YOSHIMURA Mamiko

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    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

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  • 結核菌の休眠誘導と潜伏感染成立/回避の分子機構

    Grant number：18018036

    2006 - 2007

    System name：科学研究費助成事業

    Research category：特定領域研究

    Awarding organization：日本学術振興会

    松本 壮吉, 吉村 満美子, 小林 和夫

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    Grant amount：\7300000 （ Direct Cost: \7300000 ）

    1,遺伝子転写制御の網羅的解析
    対数増殖期と定常期の野生株およびMDP1欠失株からRNAを抽出し,Mycobacterium smegmatisMC^2155株全遺伝子を標的としたDNAマイクロアレイ解析を行った。対数増殖期から定常期にかけて,既知遺伝子中,181遺伝子が増減し,そのうちの99遺伝子の発現が減衰,82遺伝子が上昇していた。野生株とMDP1欠失株の発現を比較することで,MDP1は既知遺伝子中,171遺伝子の発現制御に関わり,134遺伝子の発現抑制と34遺伝子の発現増強に関わることが明らかになった。特筆すべき点としては,定常期において高分子合成に関わる酵素の発現が終息するが,その終息にMDP1が強く関わることが判明した。
    2,蛋白質発現調節の網羅的解析
    野生株,MDP1の欠失菌,MDP1入れ戻し株の蛋白質発現パターンの違いを二次元電気泳動により比較した。MDP1欠失株は定常期以降死滅しやすく,Mycobacterium smegmatisの死滅にともない顕著に増加する蛋白質二種が認められた。質量分析により細胞壁合成に関わる脱水素酵素と分子シャペロンであった。また死滅以前にMDP1の欠失により顕著に発現変化のみられる蛋白質が少なくとも複数あることが蛋白質二次元電気泳動によっても判明した。アルコール脱水素酵素など,転写レベル(マイクロアレイ)の解析と一致するものとそうでないものが存在した。

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  • 結核菌のヒストン様蛋白質MDP1による菌の休眼誘導と潜伏感染成立/回避の分子機構

    Grant number：17019059

    2005

    System name：科学研究費助成事業

    Research category：特定領域研究

    Awarding organization：日本学術振興会

    松本 壮吉

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    Grant amount：\2500000 （ Direct Cost: \2500000 ）

    本研究は抗酸菌に特異的な核酸結合性蛋白質MDP1が標的として制御する遺伝子群やMDP1の転写抑制を免れ休眠期でも発現する遺伝子群(休眠維持分子)、MDP1の翻訳後活性に作用する分子群、すなわち定常期から休眠導入期にかけてMDP1を活性化する分子(休眠導入分子)、また休眠期から増殖期にかけてMDP1を不活化する分子(休眠解除分子)を全ゲノムレベルで同定し、結核菌の休眠導入-維持-解除の分子機構を解明することを最終の目的としている。
    MDP1が制御する遺伝子群の同定
    MDP1欠失抗酸菌株の蛋白質の二次元電気泳動を行い、野生株のパターンと比較した。MDP1を欠失させることにより、様々な蛋白質が大量に発現されていることが明らかとなった。変化の見られた蛋白質スポットを切り出しトリプシン処理した後、質量分析機にて解析し、MDP1により発現制御される蛋白質群の同定を行った。
    休眠維持分子探索を目的とした、MDP1大量発現株の作成と解析
    弱毒牛型結核菌(BCG)のMDP1遺伝子をシャトルベクターpSO246に導入しBCGの形質転換を行うことで、MDP1を大量に発現するBCGを得た。この形質転換体の発育はMDP1によりその発育が顕著に抑制されていた。MDP1大量発現株の蛋白質発現プロファイルを二次元電気泳動法により比較検討し、MDP1の転写抑制を免れ発現する蛋白質群(休眠維持候補分子)の同定を行った。
    MDP1結合性蛋白質(休眠導入/解除候補分子)の同定
    MDP1の活性を調節する分子の同定を目的として、MDP1結合性蛋白質の同定を行った。抗MDP1抗体を産生する三種のハイブリドーマ細胞を確立し特異抗体を調整した。この抗体を用いて免疫沈降反応を行い、MDP1と結合する蛋白質が存在することを明らかにした。MDP1結合蛋白質の同定を二次元電気泳動および質量分析と、結核菌ゲノム情報を利用して行った。

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  • The molecular mechanism of host responses against cell wall components of mycobacteria

    Grant number：16590368

    2004 - 2006

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    KOBAYASHI Kazuo, MATSUMOTO Sohkichi, FUJIWARA Nagatoshi

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    Grant amount：\2800000 （ Direct Cost: \2800000 ）

    Mycobacterial diseases, including tuberculosis, leprosy, and disease due to nontuberculous mycobacteria, are the major cause of death from infectious diseases around the world. About one-third of the world population is latently infected with Mycobacterium tuberculosis. Over 8 million new cases and nearly 2 million deaths occur each year. Tuberculosis presents a significant health threat to the world. The pathogenicity of mycobacteria is related to their ability to escape killing by ingested macrophages, latent infection, and induce delayed-type hypersensitivity. This has been attributed to several components of the mycobacterial cell wall, such as surface glycolipids, lipoarabinomannan, complement activation factor, heat-shock protein, and mycobacterial DNA-binding protein. In the present study, we have focused on the molecular mechanism of host responses against cell wall components of mycobacteria, including glycopeptidolipid (GPL) of Mycobacterium avium complex (MAC) and mycobacterial DNA-binding protein 1 (MDP1). Serum anti-GPL antibody was detected in patients with MAC diseases, but not in tuberculosis and healthy individuals vaccinated with BCG (sensitivity and specificity 【greater than or equal】 90%). The levels of anti-GPL antibody reflected disease activity. The measurement of antibody to GPL is useful for both diagnosis of MAC disease and assessment of diseases activity. MDP1 participates in both slow growth and adhesion/invasion of mycobacteria into host cells. Treatment of mice with MDP1-DNA complex resulted in host defense against mycobacterial infection by the induction of interferon-g and antibody to MDP1 in the host. Collectively, surface molecules of mycobacteria exert pleiotropic activities in both the microbe and host, and thus participate in the pathogenesis of mycobacterial diseases. The better understanding of molecular pathogenesis in mycobacterial infection may open the new avenue for the development of therapeutic and prophylactic interventions.

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  • 結核菌の新規蛋白質MDP1による,菌の増殖抑制及び休眠状態誘導の機構解析

    Grant number：14770121

    2002 - 2003

    System name：科学研究費助成事業

    Research category：若手研究(B)

    Awarding organization：日本学術振興会

    松本 壮吉

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    Grant amount：\3900000 （ Direct Cost: \3900000 ）

    人類の約1/3に結核菌が潜伏感染している。多くの成人型肺結核は潜伏感染菌が原因の再燃による。現在も、毎年8百万人が結核を発病、200万人が死亡している。潜伏感染菌は、一部休眠状態で潜伏しており、既製化学療法薬に対し抵抗性である。潜伏感染菌は肺においてマクロファージのみならず、非貪食性の肺胞状細胞や繊維芽細胞にも感染している。その際結核菌は、細胞表面のムコ多糖を介して上皮細胞に接着し、侵入すると考えられている。
    私は増殖を停止した菌が大量に含有するmycobacterial DNA-binding protein、1(MDP1)を見い出し、MDP1が菌の代謝を強く抑制する分子であることを明らかにした。結核菌の休眠誘導/維持におけるMDP1の役割解析を続けている。
    一方、MDP1は菌体内のみならず、表面にも存在する。核酸との相同性から菌体表面のMDP1がムコ多糖と結合し、上皮細胞との接着に関与する可能性がある。その解析を行なった。
    その結果、MDP1は、ヘパリン、ヘパラン硫酸、コンドロイチン硫酸等と結合することが分かった。結合定数は、10^<-8>〜10^<-12>Mの範囲であった。MDP1はA549ヒト肺胞上皮細胞株に接着し、この結合はヘパリンやDNAまたは抗MDP1抗体で阻害された。細胞をムコ多糖分解酵素処理することでも結合は減衰した。BCGはA549細胞に接着したが、DNAや抗MDP1抗体はこれを阻害した。上記の結果から、菌体表面のMDP1は接着分子としての活性を有し、休眠菌の肺胞上皮細胞への接着に関わると推測された。

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  • 抗酸菌感染における気道上皮細胞応答の分子機構

    Grant number：14021108

    2002

    System name：科学研究費助成事業

    Research category：特定領域研究

    Awarding organization：日本学術振興会

    小林 和夫, 前田 伸司, 藤原 永年, 松本 壮吉

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    Grant amount：\3000000 （ Direct Cost: \3000000 ）

    結核菌など抗酸菌の宿主気道上皮細胞への接着・侵入分子機序を解明するため、細胞侵入の分子機構の解析に着手した。抗酸菌感染症の主要病変部位が呼吸器系であることから、ヒトII型肺胞上皮細胞株(A549)を標的細胞として用い、抗酸菌の接着・侵入分子機序について解析した。
    Mycobacterium bovis BCG由来宿主細胞ヘパリン結合性分子についてヘパリンカラム結合性を指標として解析したところ、BCG由来28kDa蛋白質が強い結合性を示した。28kDa蛋白質のアミノ酸配列はDNAやラミニン結合性抗酸菌由来蛋白質であるmycobacterial DNA binding protein 1 (MDP1)と相同性を示した。さらに、MDP1が気道上皮細胞表層グリコサミノグリカンの構成成分であるヘパリン、ヘパラン硫酸、ヒアルロン酸やコンドロイチン硫酸に結合することを明らかにした。添加培養1時間以内でMDP1はA549細胞質内に存在し、MDP1はA549細胞への接着・取り込みに関与していることが明らかとなった。
    気道上皮細胞は種々の刺激に応答し、宿主における外界の鋭敏な感知器(センサー)である。気道上皮細胞の感知機能は結核菌など抗酸菌感染においても例外でないと考えられる。この機構に菌因子として菌表層多機能分子が、宿主因子として気道上皮細胞が関与していることが示唆される。今後、抗酸菌-気道上皮細胞の接着・侵入の分子機構、さらに、気道上皮細胞-免疫担当細胞の細胞間相互作用を明らかにし、抗酸菌感染の初期宿主応答を解明する予定である。
    結核など抗酸菌-気道上皮細胞相互作用の分子機序を解明することは抗酸菌の宿主細胞への接着・侵入を初期段階で制御する可能性、すなわち、感染の回避や感染成立後に生ずる病変の限局化を示唆し、抗酸菌感染症における新規予防・治療戦略の開発に糸口を提供するであろう。

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  • SERA高分泌型、組み換えBCG菌の作製及び免疫原性の検討

    Grant number：14021094

    2002

    System name：科学研究費助成事業

    Research category：特定領域研究

    Awarding organization：日本学術振興会

    松本 壮吉

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    Grant amount：\3000000 （ Direct Cost: \3000000 ）

    マラリア防御抗原SERA47がBCGの細胞内に留まっている組み換えBCG菌(rBCGSERA47)を培養後細胞壁を粉砕し得た細胞破砕液をマウスに免疫した。結果、rBCGSERA47の免疫では抗SERA抗体は誘導されないが、その細胞破砕液投与では、抗SERA抗体の上昇が認められた。このことから、菌体外にSERAを分泌する必要が考えられた。SERA47は中央にセリンの繰り返し配列を除く事で(SERA36)大腸菌での産生および分泌障害が改善されることが示唆されている。それでBCGからのSERA36発現を試みた。SERA47の発現構築と同様に構築し、BCGの形質転換を行ったが、SERA36の発現および分泌は全く認められなかった。キャリアーとして用いているalpha-抗原とSERAとの融合蛋白質の構造の問題が発現障害を起こしている可能性が示唆されるため、現在、alpha-抗原の立体構造解析結果を基にキャリアー蛋白質の構造を壊さない部位への挿入を計画し実験を進めており、Mycobacterium smegmatisからの分泌に成功した。
    昨年作製したrBCG-MSP1Cをマウスに免疫した。組み換えBCG単独では、顕著な抗体産生が認められなかった。Plasmodium yoelii(マウスマラリア原虫)由来のMSP1の場合、組み換えBCG単独免疫では抗MSP1抗体が上昇せず、原虫感染後に抗体価の上昇が見られた。同様の免疫効果がPlasmodium falciparum由来のMSP1を用いても生じている可能性を検討した。大腸菌で発現させ得られた組み換え蛋白質(MSP1)を追加免疫すると、rBCG-MSP1C免疫群のマウスでのみ抗MSP1抗体の上昇が確認された。この結果から、この組み換えBCGで免疫しておくと、P. falciparumが感染した場合速やかに抗MSP1抗体が産生される可能性が示唆された。

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  • ヒトマラリアの防御抗原を発現する組み換えBCGワクチンの作製

    Grant number：13226100

    2001

    System name：科学研究費助成事業

    Research category：特定領域研究(C)

    Awarding organization：日本学術振興会

    松本 壮吉

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    1.これまでに組み換えBCGのシステムを用いてPlasmodium falciparumのMSP1のC末端部をコードする遺伝子を組み入れた組み換えBCG菌を作製し、BCG菌からのMSP1-Cの分泌を確認した。またその構造は本来の立体構造に近い構造をとっていることも分かった。しかしながら分泌量に関してはまだ十分ではないことから、この抗原により誘導される防御免疫を高めるのは難しいものと考えられた。今回、発現量を増加させる対策として、MSP1-Cの遺伝子のコドンを抗酸菌型のコドンに適合させた人工の合成遺伝子を作製した。この合成遺伝子を用いて上記と同様にして組み換えBCG菌を作製し、BCGからのMSP1-Cの分泌量を検討したところ分泌量が上昇しているのが確認された。またMSP1-Cの発現領域を修正することによりBCGからの分泌量をさらに増加させることができた。
    2.SERA(SE47')は我々の発現システムを用いた場合、大量分泌系には適さない可能性が示されたことから、今回ストレス蛋白質であるHSP60及びα-crystallin like proteinのプロモーターを用いて菌体内の発現を目指した新しいベクターの構築を行い、BCGを形質転換した。得られた組み換えBCG菌からのSE47'の発現を検討したところ、BCG菌体内でのSE47'の発現が確認された。菌体内での発現はα-crystallin like proteinのプロモーターを用いた場合においてより多く発現しているのが確認された。次に、SE47'の発現が確認された組み換えBCG菌をマウスに投与し、抗体産生誘導能について検討した初回免疫後4週、8週、21週後の抗血清を用いて抗SE47'抗体価をABC-ELISA法で測定したところ、抗体価の上昇は認められなかった。

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  • 組み換えBCGワクチンシステムを用いた、う蝕予防ワクチンの開発

    Grant number：11771116

    1999

    System name：科学研究費助成事業

    Research category：奨励研究(A)

    Awarding organization：日本学術振興会

    松本 壮吉

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    Grant amount：\1100000 （ Direct Cost: \1100000 ）

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  • SERAを発現する組み換えBCGワクチンの作製及び防御効果の検討

    Grant number：11147223

    1999

    System name：科学研究費助成事業

    Research category：特定領域研究(A)

    Awarding organization：日本学術振興会

    山田 毅, 松本 壮吉

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    Grant amount：\1700000 （ Direct Cost: \1700000 ）

    (研究の目的)マラリアのワクチン抗原として様々な分子が同定され、ワクチン開発がなされている。その抗原の効果を引き出すのにアジュバントが必要であるが、ヒトに応用可能なアジュバントはまだ十分に開発されていない。結核の予防ワクチンBCG菌はヒトに使用できるアジュバントの中で最大の活性をもし安全性も高い。我々は、抗酸菌の分泌蛋白質α抗原をキャリアーとして外来蛋白質をBCGから分泌させるシステムを作製した。このシステムを用いてネズミマラリアの系で赤内型マラリア原虫の感染防御に成功した。このシステムをヒトに応用するため、ヒト型のP.falciparumの防御抗原SERAをBCG菌から大量に発現分泌させることを試みた。
    (今年度の成果及び考察)1.これまでにP.falciparumの防御抗原SERA(SE47')をコードする合成遺伝子全体とN末端部(SE47'-N),C末端部(SE47'-C)に二分割した断片をそれぞれα抗原遺伝子内に挿入し、組み換えBCGを作製した。それらを培養後、培養上清中の蛋白質にSE47'が分泌されていることを確認した。その結果、培養上清中に、SE47'の存在を確認することができた。
    2.次ぎに、SE47'の発現が確認された組み換えBCGをマウスに免疫し、抗体産生誘導能について検討した。マウスは6週令のBALB/c,♀を用いた。組み換えBCGをマウスの皮下に3回接種し、最終免疫後10日目に抗血清を採取した。そして抗SE47'抗体価をABC-ELISA法で測定したところ、400倍希釈で抗SE47'抗体の産生が認められた。

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  • マラリアのワクチン開発を目指した,BCGからのSERA抗原発現の試み

    Grant number：10166218

    1998

    System name：科学研究費助成事業

    Research category：特定領域研究(A)

    Awarding organization：日本学術振興会

    山田 毅, 内藤 真理子, 松本 壮吉, 大原 直也

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    Grant amount：\1500000 （ Direct Cost: \1500000 ）

    マラリアワクチン開発で,最も障害となっているのがアジュバントの問題である.動物実験等で,防御効果が確認されている抗原を,実際にヒトに投与するには,安全性と有効性を兼ね備えたアジュバントが必要であるが,未だ十分なものが無い.我々は熱帯医学研究所神原廣二教授との共同研究で,組み換えBCGのシステムを用いて,マウスを用いた赤内型マラリア原虫感染防御に成功し,その防御機構が,細胞性免疫をベースにした防御抗体産生誘導であることを,数年にわたる解析の結果,明らかにし,本年発表した(J.Exp.Med.,1998).さらに,BCGシステムを,ヒトに応用するため,熱帯熱マラリアの防御抗原SERAをα抗原をキャリアーとしてBCGから発現させることを試みた.SERAをコードする合成遺伝子をα抗原遺伝子の様々な場所に挿入し,合計7種類の組み換えBCGを作製した.それらを,試験管内で培養し,分泌抗原中の蛋白質を解析してきたが,現在までの所,十分量のSERA抗原を発現する,組み換えBCG菌は得られていない.この原因は,1;発現させるのにSERAの分子量が大きすぎる,2;SERA抗原の一定部位が分泌に適さない(不溶体を形成する),3;使用コドンの不適合,4;プロモーター活性が低い等の原因が考えられた.現在1,2の原因を解決すべく,SERA遺伝子を分割して,発現させることを試みている.また,α抗原以外のキャリアー蛋白質の検討を行い,抗体産生能の高いMDP1等の抗原とSERAの融合蛋白質を発現させる,プラスミッドを構築している.

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  • A study for non-specific or specific immunochemotherapy by using recombinant BCG

    Grant number：09672056

    1997 - 2000

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    MATSUO Takemitsu, NAITO Mariko, OHARA Naoya

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    Grant amount：\3300000 （ Direct Cost: \3300000 ）

    Mycobacterium bovis BCG (BCG) secrete different antigenic proteins. The amount and anti-tumor effects depend on BCG substrains. BCG has not only a direct anti-tumor effects but also indirect effects mediated macrophages. In order to study for an anti-cancer immuno-chemotherapy by using recombinant BCG, first we studied expression mechanisms, regulatory factors, and DNA binding proteins. Secondly we examined direct anti-tumor effects. Finally we investigated indirect anti-tumor effects mediated macrophages.
    BCG substrain Tokyo (BCG Tokyo) secrete a large amount of the MPB70 protein, whereas BCG substrain Pasteur secrete little. The MPB70 genes in two substrains showed exactly the same sequence, and regulated transcriptional stage. We confirmed DNA binding proteins by gel shift assay, then extracted a 20 kDa protein, and confirmed a single strand DNA binding protein.
    We prepared culture filtrate (CF) and cell lysate (Ly) by BCG Tokyo, then measured anti-tumor effects. The cell growth was measured by the human squamous cell carcinoma cell line (SCC-25) and human gingival fibroblast cell line (HGF). CF and Ly dose-dependently inhibited the cell growth of SCC-25. The inhibition effect of CF was higher than that of Ly and the anti-tumor effect of CF was also greater.
    For an indirect anti-tumor effects mediating macrophages, we examined the secreted proteins of BCG released to the cytoplasm from the phagosome by BCG infected macrophages. The MPB70 protein was shown only the phagosomal fraction. We suppose the MPB70 protein released to the cytoplasm from the phagosome. Same result was observed for BCG infected SCC-25. Usually, bacteria were phagocyted by macrophage and fragmented into peptides in phagosome. These peptides bound to MHC class II molecules. But it was thought that the proteins released to the cytoplasm are fragmented peptides and bound to MHC class I molecules. According to exam, possibility was suggested to make CTLs activate much more.

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  • 歯周病関連菌由来,ストレス蛋白質の免疫学的研究

    Grant number：08771579

    1996

    System name：科学研究費助成事業

    Research category：奨励研究(A)

    Awarding organization：日本学術振興会

    松本 壮吉

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    Grant amount：\1100000 （ Direct Cost: \1100000 ）

    我々は,ヒトの70キロダルトン(kDa)熱ショック蛋白質に相同性のある蛋白質の遺伝子をA.actinomycetecomcomitans(A.a.)の染色体より,その遺伝子を含む,2696bpのDNAフラグメントをクローニングし,その全塩基配列を決定した.これらの結果,以下のことが分かった.A.a.の70kDa蛋白質は,大腸菌の70kDa熱ショック蛋白質(DnaK)とアミノ酸で,83%の相同性があることが分かった.また,大腸菌のdna K遺伝子のプロモーター配列と相同の配列が,70kDa蛋白質遺伝子上流に存在した.クローニングしたDNAフラグメントには,70kDa熱ショック蛋白質以外に,40キロダルトン熱ショック蛋白質と相同性の高い蛋白質が,70kDa蛋白質遺伝子の下流に存在することが分かった.また,70kDaと40kDaをコードする遺伝子間に,400bp程のスペースシーケンスがあり,そこには,逆方向繰り返し配列が複数存在した.我々は,本年度70kDa蛋白質及び,40kDa蛋白質が熱ショックにより,発現が増強されることを,本年度,特異抗体を作成して確認したが,このA.a.に特異的な染色体構造が,70kDa及び40kDa蛋白質の発現調節に関与している可能性について,現在検討している.また,70kDa蛋白質の,歯周疾患との関連を検討するため,70kDa蛋白質遺伝子を,発現用プラスミッドに挿入し,大腸菌で,大量に発現させ,その産物をカラムを用いて精製した.それを用い,ELISA法にて,患者血清中に70kDaに対する,抗体が存在することを確認した.今後,歯周病の惹起及び憎悪に,ストレス蛋白質に対する宿主(ヒト)の免疫応答がどのように関与しているかを検討していきたい.

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  • A.actinomycetecomcomitansの熱ショック蛋白質の研究

    Grant number：07771620

    1995

    System name：科学研究費助成事業

    Research category：奨励研究(A)

    Awarding organization：日本学術振興会

    松本 壮吉

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    Grant amount：\800000 （ Direct Cost: \800000 ）

    我々は,A.actinomycetecomcomitans(A.a.)の染色体より,大腸菌の主要な熱ショック蛋白質,Dna K及び,ヒトの70kDa熱ショック蛋白質に相同性のある蛋白質の遺伝子を含む,2696bpのDNAフラグメントをクローニングし,その全塩基配列を決定した.この,DNAフラグメントには,70kDa熱ショック蛋白質以外に,大腸菌の熱ショック蛋白質Dna Jと相同性の高い蛋白質の,アミノ末端領域の塩基配列が見つかった.それは,70kDa蛋白質遺伝子の,カルボ末端側に存在していた.dna J遺伝子の上流には,プロモーターと考えられる塩基配列がなく,この2つの遺伝子は,一つのオペロンとして転写されるものと考えられた.70kDa蛋白質の遺伝子のアミノ末端が,一部,含まれていなかったため,上流領域の遺伝子のクローニングを試み,それをコードする遺伝子断片を含む,約3kbpのDNAフラグメントをクローニングし,その塩基配列を決定した.その結果,A.a.の70kDa蛋白質は,大腸菌のDna Kとアミノ酸で,83%の相同性があることが分かった.また,大腸菌のdna K遺伝子のプロモーター配列と似た配列が,70kDa蛋白質遺伝子上流に存在し,プロモーター配列と考えられた.それは,大腸菌でも認識される可能性が考えられたため,我々は,70kDa熱ショック蛋白質をコードする遺伝子,およびそのプロモーター配列を含むと考えられるDNA断片を,大腸菌のプラスミッドに挿入し,大腸菌内で発現するかどうかを検討したが,その発現は,検出できなかった.70kDa蛋白質の,歯周疾患との関連を検討するため,70kDa蛋白質を,発現用プラスミッドを用いて,大量に発現させ,その産物をカラムを用いて精製した.現在,患者由来のTリンパ球との反応を,免疫学的手法により検討中である.

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  • A.actinomycetemcomitansの熱ショック蛋白質の研究

    Grant number：06771600

    1994

    System name：科学研究費助成事業

    Research category：奨励研究(A)

    Awarding organization：日本学術振興会

    松本 壮吉

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    Grant amount：\1000000 （ Direct Cost: \1000000 ）

    まずターゲットとしたActinobacillus actinomycetemcomitans(A.a.)の様々な蛋白質のアミノ酸コドンの使用頻度を遺伝子バンクより検証しそれぞれのアミノ酸の最頻用コドンを特定した.次に,既にクローニングされ塩基配列の決定された他菌種の70kDaヒートショック蛋白質のデータを基に,保存された領域を検索し,最頻用コドンのデータを考慮しA.a.の70kDaヒートショック蛋白質特異的なDNAプローブを作成した.それを用いてA.a.ゲノムを鋳型にしてPCR法を行い,予想されたサイズ(およそ400bp)に増幅されたPCR産物をクローニングし塩基配列の決定を行った.その結果大腸菌由来の70kDaヒートショック蛋白質(Dna K)とDNAで53%,アミノ酸で83%の相同性を示しA.a.由来70kDaヒートショック蛋白質遺伝子が増幅されていることが分かった.次に,得られた400bpフラグメントをプローブにしてA.a.染色体を制限酵素Hind III,Spe I,Acc Iで切断しサザンハイブリダイゼイションを行った.15.0kbp(Hind III),10.0kbp(Spe I),4.0kbp(Acc I)の位置に反応する単一のバンドを確認した.(以上の結果は,歯科基礎医学会,平成10月17,18日に発表)次に,A.a.ゲノムをSpe Iで切断し,電気泳動後10.0kbpを抽出し精製した.これを大腸菌用クローニングヴェクターに挿入し遺伝子ライブラリーを作成した.コロニーハイブリダイゼイション法により70kDaヒートショック蛋白質遺伝子を含むDNAフラグメントをクローニングした.現在,それの塩基配列を決定中である.

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  • Study of antigenic proteins of mycobacteria

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    Grant type：Competitive

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  • Development of malaria vaccine

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    Grant type：Competitive

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  • Study of artigenic proteins of the microbiol of periodontal disease

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    Grant type：Competitive

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Teaching Experience (researchmap)

  • 細菌学

    Institution name：新潟大学医学部、大阪市立大学医学部

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Teaching Experience

  • 先端医科学研究概説

    2022
    -
    2023
    Institution name：新潟大学

  • 微生物学Ⅰ

    2018
    -
    2023
    Institution name：新潟大学

  • 感染と免疫

    2015
    Institution name：新潟大学

  • 微生物学Ⅰ・Ⅱ

    2015
    Institution name：新潟大学

  • 生体防御と感染(細菌学)

    2014
    Institution name：新潟大学