Updated on 2025/09/10

写真a

 
NISHIYAMA Akihito
 
Organization
Academic Assembly Institute of Medicine and Dentistry IGAKU KEIRETU Lecturer
Graduate School of Medical and Dental Sciences Community Disease Control Lecturer
Title
Lecturer
Homepage
https://www.med-niigatauniv-bacteriol.org
External link

The Best Research Achievement in Research Career

    • 【Papers】 Dynamic action of an intrinsically disordered protein in DNA compaction that induces mycobacterial dormancy.  2023.12

    • 【Papers】 Adduct Formation of Delamanid with NAD in Mycobacteria  2020.3

    • 【Papers】 C-terminal intrinsically disordered region-dependent organization of the mycobacterial genome by a histone-like protein  2018.12

Degree

  • 博士（農学） ( 2003.3   東北大学 )

Research Interests

  • tuberculosis

  • bacteriology

Research Areas

  • Life Science / Bacteriology

Research History (researchmap)

  • Niigata University   Department of Bacteriology, School of Medicine   Lecturer

    2010.7

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  • Niigata University   Department of Bacteriology, School of Medicine   Assistant Professor

    2007.3 - 2010.6

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  • Florida Atlantic University   Charles E. Schmidt College of Biomedical Sciences   Research Associate

    2003.9 - 2007.1

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  • East Carolina University   Department of Physiology, the Brody School of Medicine   Research Associate

    2003.6 - 2003.9

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Research History

  • Niigata University   Graduate School of Medical and Dental Sciences Community Disease Control   Lecturer

    2010.7

  • Niigata University   Graduate School of Medical and Dental Sciences Community Disease Control   Assistant Professor

    2007.3 - 2010.6

Education

  • Tohoku University   Graduate School of Agricultural Science   Department of Molecular and Cellular Biology

    2000.4 - 2003.3

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  • Tohoku University   Graduate School of Agricultural Science   Department of Molecular and Cellular Biology

    1998.4 - 2000.3

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  • Tohoku University   Faculty of Agriculture   Applied Biological Chemistry

    1994.4 - 1998.3

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Professional Memberships

  • American Society for Microbiology

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  • JAPAN SOCIETY FOR BIOSCIENCE, BIOTECHNOLOGY, AND AGROCHEMISTRY

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  • JAPANESE SOCIETY FOR BACTERIOLOGY

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Studying abroad experiences

  • フロリダ・アトランティック大学生物医学部（Charles E. Schmidt College of Biomedical Sciences, Florida Atlantic University）、米国   博士研究員

    2003.9 - 2007.1

  • イースト・カロライナ大学医学部（Brody School of Medicine at East Carolina University）, 米国   博士研究員

    2003.6 - 2003.9

 

Papers

  • 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)  

    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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  • 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 Reviewed

    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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    Language：English   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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  • Dynamic action of an intrinsically disordered protein in DNA compaction that induces mycobacterial dormancy. Reviewed 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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    Language：English   Publishing type：Research paper (scientific journal)  

    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 Reviewed

    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   681   111 - 119   2023.9

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

    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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  • Monitoring IgG against <i>Mycobacterium tuberculosis</i> proteins in an Asian elephant cured of tuberculosis that developed from long-term latency Reviewed 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   2022.12

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

    Abstract

    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.

    DOI： 10.1038/s41598-022-08228-7

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    Other Link： https://www.nature.com/articles/s41598-022-08228-7

  • Lysocin E Targeting Menaquinone in the Membrane of Mycobacterium tuberculosis Is a Promising Lead Compound for Antituberculosis Drugs. Reviewed 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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  • Identification and functional analysis of a new type of <i>Z,E</i> ‐mixed prenyl reductase from mycobacteria Reviewed International journal

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

    The FEBS Journal   289 ( 16 )   4981 - 4997   2022.3

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

    Isoprenoids with reduced Z,E-mixed prenyl groups are found in various organisms. To date, only polyprenol reductases (PR-Dol) involved in dolichol biosynthesis have been identified as enzymes capable of reducing Z,E-mixed prenyl groups. Although C35 -isoprenoids with reduced Z,E-mixed prenyl groups are found in mycobacteria, Z,E-mixed heptaprenyl reductase (HepR) remains unidentified. In the present study, the identification and functional analysis of HepR was performed. No PR-Dol homolog gene was detected in the genome of Mycolicibacterium vanbaalenii. However, a homolog of geranylgeranyl reductase (GGR), which reacts with an all-E prenyl group as a substrate, was encoded in the genome; thus, we analyzed it as a HepR candidate. In vitro enzymatic assay and in vivo gene suppression analysis identified the GGR homolog as HepR and revealed that HepR catalyzes the reduction of ω- and E- prenyl units in Z,E-mixed heptaprenyl diphosphates, and C35 -isoprenoids are mainly biosynthesized using E,E,E-geranylgeranyl diphosphate as a precursor. Thus, it was demonstrated that the Z,E-mixed prenyl reductase family exists in the GGR homologs. To the best of our knowledge, this is the first identification of a new type of Z,E-mixed prenyl reductase with no sequence homology to PR-Dol. The substrate specificity of HepR significantly differed from that of GGR, suggesting that it is a new enzyme. HepR homologs are widely distributed in mycobacterial genomes, and lipid analysis suggests that many strains, including pathogenic species, produce HepR metabolites. The discovery of this new enzyme will promote further research on Z,E-mixed isoprenoids.

    DOI： 10.1111/febs.16412

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    Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/febs.16412

  • 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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    Language：English   Publisher：日本細菌学会  

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

    Ilinov A, Nishiyama A, Namba H, Fukushima Y, Takihara H, Nakajima C, Savitskaya A, Gebretsadik G, Hakamata M, Ozeki Y, Tateishi Y, Okuda S, Suzuki Y, Vinnik YS, Matsumoto S

    Scientific Reports   11 ( 1 )   10953 - 10953   2021.5

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    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 Mycobacterium tuberculosis, M. intracellulare, and M. avium 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 M. tuberculosis and M. intracellulare. In contrast, accumulation of phage DNA in eDNA of M. avium, 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.

    DOI： 10.1038/s41598-021-90156-z

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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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    Language：Japanese   Publisher：(一社)日本結核・非結核性抗酸菌症学会  

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  • Comparative genomic analysis of Mycobacterium intracellulare: Implications for clinical taxonomic classification in pulmonary Mycobacterium avium-intracellulare complex disease Reviewed

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

    BMC Microbiology   In press   2021.3

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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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  • 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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  • 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 Reviewed

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

    Scientific Reports   10 ( 1 )   5449   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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    Other Link： http://www.nature.com/articles/s41598-020-62287-2

  • Higher genome mutation rates of Beijing lineage of Mycobacterium tuberculosis during human infection Reviewed 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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    <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.

    DOI： 10.1038/s41598-020-75028-2

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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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  • 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 )   2020.3

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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.

    DOI： 10.1128/aac.01755-19

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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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  • 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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  • 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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  • 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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  • 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   2018.10

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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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  • 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   6810   2017.7

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    DOI： 10.1038/s41598-017-06480-w

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  • Emergence of Panton-Valentine leukocidin-positive ST59 methicillin-susceptible Staphylococcus aureus with high cytolytic peptide expression in association with community-acquired pediatric osteomyelitis complicated by pulmonary embolism Reviewed

    Emi Sawanobori, Wei-Chun Hung, Tomomi Takano, Koji Hachuda, Tadahiro Horiuchi, Wataru Higuchi, Wei-Wen Hung, Yasuhisa Iwao, Akihito Nishiyama, Ivan Reva, Galina Reva, Lee-Jene Teng, Tatsuo Yamamoto

    JOURNAL OF MICROBIOLOGY IMMUNOLOGY AND INFECTION   48 ( 5 )   565 - 573   2015.10

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    DOI： 10.1016/j.jmii.2014.04.015

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  • Elderly infection in the community due to ST5/SCCmecII methicillin-resistant Staphylococcus aureus (the New York/Japan clone) in Japan: Panton-Valentine leukocidin-negative necrotizing pneumonia Reviewed

    Olga Khokhlova, Yusuke Tomita, Wei-Chun Hung, Tomomi Takano, Yasuhisa Iwao, Wataru Higuchi, Akihito Nishiyama, Ivan Reva, Tatsuo Yamamoto

    JOURNAL OF MICROBIOLOGY IMMUNOLOGY AND INFECTION   48 ( 3 )   335 - 339   2015.6

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    DOI： 10.1016/j.jmii.2012.09.004

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  • Virulence gene and expression analysis of community-associated methicillin-resistant Staphylococcus aureus causing iliopsoas abscess and discitis with thrombocytopenia Reviewed

    Wei-Chun Hung, Hiromitsu Mori, Sayaka Tsuji, Yasuhisa Iwao, Tomomi Takano, Akihito Nishiyama, Ivan Reva, Tatsuo Yamamoto

    JOURNAL OF INFECTION AND CHEMOTHERAPY   19 ( 5 )   1004 - 1008   2013.10

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    DOI： 10.1007/s10156-013-0561-5

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  • A new local variant (ST764) of the globally disseminated ST5 lineage of hospital-associated methicillin-resistant Staphylococcus aureus (MRSA) carrying the virulence determinants of community-associated MRSA Reviewed

    Tomomi Takano, Wei-Chun Hung, Michiko Shibuya, Wataru Higuchi, Yasuhisa Iwao, Akihito Nishiyama, Ivan Reva, Olga E. Khokhlova, Shizuka Yabe, Kyoko Ozaki, Misao Takano, Tatsuo Yamamoto

    Antimicrobial Agents and Chemotherapy   57 ( 4 )   1589 - 1595   2013.4

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    DOI： 10.1128/AAC.01147-12

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  • Genetic nature and virulence of community-associated methicillin-resistant Staphylococcus aureus Invited Reviewed

    Tatsuo Yamamoto, Wei-Chun Hung, Tomomi Takano, Akihito Nishiyama

    BioMedicine (Netherlands)   3 ( 1 )   2 - 18   2013.3

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    DOI： 10.1016/j.biomed.2012.12.001

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  • Recurrence of pelvic abscess from PantonValentine leukocidin-positive community-acquired ST30 methicillin-resistant Staphylococcus aureus Reviewed

    Hirokazu Isobe, Dai Miyasaka, Tomoyuki Ito, Tomomi Takano, Akihito Nishiyama, Yasuhisa Iwao, Olga E. Khokhlova, Takeshi Okubo, Naoto Endo, Tatsuo Yamamoto

    PEDIATRICS INTERNATIONAL   55 ( 1 )   120 - 123   2013.2

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    DOI： 10.1111/j.1442-200X.2012.03612.x

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  • Anti-Helicobacter pylori actions of CV-6209, a platelet-activating factor receptor antagonist Reviewed

    Yasuhisa Iwao, Tomomi Takano, Ikue Taneike, Ivan Reva, Hirokazu Isobe, Hui-Min Zhang, Akihito Nishiyama, Tatsuo Yamamoto

    JOURNAL OF GENERAL AND APPLIED MICROBIOLOGY   59 ( 2 )   147 - 152   2013

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  • Accumulation of staphylococcal Panton-Valentine leukocidin in the detergent-resistant membrane microdomains on the target cells is essential for its cytotoxicity Reviewed

    Akihito Nishiyama, Hirokazu Isobe, Yasuhisa Iwao, Tomomi Takano, Wei-Chun Hung, Ikue Taneike, Saori Nakagawa, Soshi Dohmae, Nobuhiro Iwakura, Tatsuo Yamamoto

    FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY   66 ( 3 )   343 - 352   2012.12

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    DOI： 10.1111/j.1574-695X.2012.01027.x

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  • Evolution and virulence of Panton-Valentine leukocidin-positive ST30 methicillin-resistant Staphylococcus aureus in the past 30 years in Japan Reviewed

    Hirokazu Isobe, Tomomi Takano, Akihito Nishiyama, Wei-Chun Hung, Shuichi Kuniyuki, Yasuhiro Shibuya, Ivan Reva, Shizuka Yabe, Yasuhisa Iwao, Wataru Higuchi, Olga E. Khokhlova, Takeshi Okubo, Tatsuo Yamamoto

    BIOMEDICAL RESEARCH-TOKYO   33 ( 2 )   97 - 109   2012.4

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    DOI： 10.2220/biomedres.33.97

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  • Super-sticky familial infections caused by Panton-Valentine leukocidin-positive ST22 community-acquired methicillin-resistant Staphylococcus aureus in Japan Reviewed

    Tatsuo Yamamoto, Tomomi Takano, Shizuka Yabe, Wataru Higuchi, Yasuhisa Iwao, Hirokazu Isobe, Kyoko Ozaki, Misao Takano, Ivan Reva, Akihito Nishiyama

    JOURNAL OF INFECTION AND CHEMOTHERAPY   18 ( 2 )   187 - 198   2012.4

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    DOI： 10.1007/s10156-011-0316-0

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  • The emerging ST8 methicillin-resistant Staphylococcus aureus clone in the community in Japan: associated infections, genetic diversity, and comparative genomics Reviewed

    Yasuhisa Iwao, Rumiko Ishii, Yusuke Tomita, Yasuhiro Shibuya, Tomomi Takano, Wei-Chun Hung, Wataru Higuchi, Hirokazu Isobe, Akihito Nishiyama, Mio Yano, Tetsuya Matsumoto, Kikuyo Ogata, Takeshi Okubo, Olga Khokhlova, Pak-Leung Ho, Tatsuo Yamamoto

    JOURNAL OF INFECTION AND CHEMOTHERAPY   18 ( 2 )   228 - 240   2012.4

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    DOI： 10.1007/s10156-012-0379-6

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  • Reduction of Overall Helicobacter pylori Colonization Levels in the Stomach of Mongolian Gerbil by Lactobacillus johnsonii La1 (LC1) and Its in Vitro Activities against H. pylori Motility and Adherence Reviewed

    Hirokazu Isobe, Akihito Nishiyama, Tomomi Takano, Wataru Higuchi, Saori Nakagawa, Ikue Taneike, Yoichi Fukushima, Tatsuo Yamamoto

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   76 ( 4 )   850 - 852   2012.4

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    DOI： 10.1271/bbb.110921

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  • Isolation and molecular characterization of methicillin-resistant Staphylococcus aureus from public transport Reviewed

    Yasuhisa Iwao, Shizuka Yabe, Tomomi Takano, Wataru Higuchi, Akihito Nishiyama, Tatsuo Yamamoto

    MICROBIOLOGY AND IMMUNOLOGY   56 ( 1 )   76 - 82   2012.1

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    DOI： 10.1111/j.1348-0421.2011.00397.x

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  • Helicobacter pylori Eradication by Sitafloxacin-Lansoprazole Combination and Sitafloxacin Pharmacokinetics in Mongolian Gerbils and Its In Vitro Activity and Resistance Development Reviewed

    Tatsuo Yamamoto, Tomomi Takano, Wataru Higuchi, Akihito Nishiyama, Ikue Taneike, Kumi Yoshida, Hiroko Kanda, Yuichiro Imamura

    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY   55 ( 9 )   4261 - 4266   2011.9

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    DOI： 10.1128/AAC.01105-10

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  • Chitin particles induce size-dependent but carbohydrate-independent innate eosinophilia Reviewed

    Mari Kogiso, Akihito Nishiyama, Tsutomu Shinohara, Masataka Nakamura, Emiko Mizoguchi, Yoshinori Misawa, Elisabeth Guinet, Mahyar Nouri-Shirazi, C. Kathleen Dorey, Ruth Ann Henriksen, Yoshimi Shibata

    JOURNAL OF LEUKOCYTE BIOLOGY   90 ( 1 )   167 - 176   2011.7

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    DOI： 10.1189/jlb.1110624

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  • Emergence of the community-acquired methicillin-resistant Staphylococcus aureus USA300 clone in a Japanese child, demonstrating multiple divergent strains in Japan Reviewed

    Wataru Higuchi, Shigenao Mimura, Yoshihiro Kurosawa, Tomomi Takano, Yasuhisa Iwao, Shizuka Yabe, Olga Razvina, Akihito Nishiyama, Yurika Ikeda-Dantsuji, Fuminori Sakai, Hideaki Hanaki, Tatsuo Yamamoto

    JOURNAL OF INFECTION AND CHEMOTHERAPY   16 ( 4 )   292 - 297   2010.8

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    DOI： 10.1007/s10156-010-0051-y

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  • Community-acquired methicillin-resistant Staphylococcus aureus: community transmission, pathogenesis, and drug resistance Invited Reviewed

    Tatsuo Yamamoto, Akihito Nishiyama, Tomomi Takano, Shizuka Yabe, Wataru Higuchi, Olga Razvina, Da Shi

    JOURNAL OF INFECTION AND CHEMOTHERAPY   16 ( 4 )   225 - 254   2010.8

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    DOI： 10.1007/s10156-010-0045-9

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  • Molecular typing of Campylobacter jejuni and C-coli from chickens and patients with gastritis or Guillain-Barre syndrome based on multilocus sequence types and pulsed-field gel electrophoresis patterns Reviewed

    Shizuka Yabe, Wataru Higuchi, Yasuhisa Iwao, Tomomi Takano, Olga Razvina, Ivan Reva, Akihito Nishiyama, Tatsuo Yamamoto

    MICROBIOLOGY AND IMMUNOLOGY   54 ( 6 )   362 - 367   2010.6

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    DOI： 10.1111/j.1348-0421.2010.00222.x

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  • Streptococcus pneumoniae and Haemophilus influenzae at the initial stage of influenza Reviewed

    Misao Takano, Kyoko Ozaki, Yoshiyuki Nitahara, Wataru Higuchi, Tomomi Takano, Akihito Nishiyama, Tatsuo Yamamoto

    PEDIATRICS INTERNATIONAL   51 ( 5 )   687 - 695   2009.10

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    DOI： 10.1111/j.1442-200X.2009.02861.x

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  • Capture of heat-killed Mycobacterium bovis bacillus Calmette-Guerin by intelectin-1 deposited on cell surfaces Reviewed

    Shoutaro Tsuji, Makiko Yamashita, Donald R. Hoffman, Akihito Nishiyama, Tsutomu Shinohara, Takashi Ohtsu, Yoshimi Shibata

    GLYCOBIOLOGY   19 ( 5 )   518 - 526   2009.5

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    DOI： 10.1093/glycob/cwp013

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  • Genotypes, intrafamilial transmission, and virulence potential of nasal methicillin-resistant Staphylococcus aureus from children in the community Reviewed

    Kyoko Ozaki, Misao Takano, Wataru Higuchi, Tomomi Takano, Shizuka Yabe, Yoshiyuki Nitahara, Akihito Nishiyama, Tatsuo Yamamoto

    JOURNAL OF INFECTION AND CHEMOTHERAPY   15 ( 2 )   84 - 91   2009.4

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    DOI： 10.1007/s10156-009-0668-x

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  • A rapid screening method for Panton-Valentine leucocidin-positive community-acquired methicillin-resistant Staphylococcus aureus belonging to multilocus sequence type 30 and its related clone using a combination of multiplex PCR and pulsed-field gel electrophoresis Reviewed

    Ivan Reva, Wataru Higuchi, Tomomi Takano, Olga Singur, Kyoko Ozaki, Hirokazu Isobe, Shizuka Yabe, Kohei Saito, Tatiana Baranovich, Symaa Enany, Taketo Otsuka, Vladimir Potapov, Akihito Nishiyama, Tatsuo Yamamoto

    JOURNAL OF INFECTION AND CHEMOTHERAPY   15 ( 2 )   75 - 83   2009.4

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    DOI： 10.1007/s10156-009-0667-y

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  • Depletion of cellular cholesterol enhances macrophage MAPK activation by chitin microparticles but not by heat-killed Mycobacterium bovis BCG Reviewed

    Akihito Nishiyama, Tsutomu Shinohara, Traci Pantuso, Shoutaro Tsuji, Makiko Yamashita, Shizuka Shinohara, Quentin N. Myrvik, Ruth Ann Henriksen, Yoshimi Shibata

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   295 ( 2 )   C341 - C349   2008.8

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    DOI： 10.1152/ajpcell.00446.2007

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  • Catalytically inactive cyclooxygenase 2 and absence of prostaglandin E-2 biosynthesis in murine peritoneal macrophages following in vivo phagocytosis of heat-killed Mycobacterium bovis bacillus Calmette-Guerin Reviewed

    Makiko Yamashita, Tsutomu Shinohara, Shoutaro Tsuji, Quentin N. Myrvik, Akihito Nishiyama, Ruth Ann Henriksen, Yoshimi Shibata

    JOURNAL OF IMMUNOLOGY   179 ( 10 )   7072 - 7078   2007.11

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    DOI： 10.4049/jimmunol.179.10.7072

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  • Differential structure and activity between human and mouse intelectin-1: Human intelectin-1 is a disulfide-linked trimer, whereas mouse homologue is a monomer Reviewed

    Shoutaro Tsuji, Makiko Yamashita, Akihito Nishiyama, Tsutomu Shinohara, Zhongwei Li, Quentin N. Myrvik, Donald R. Hoffman, Ruth Ann Henriksen, Yoshimi Shibata

    GLYCOBIOLOGY   17 ( 10 )   1045 - 1051   2007.10

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    DOI： 10.1093/gob/cwm075

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  • Differential subcellular localization of COX-2 in macrophages phagocytosing heat-killed Mycobacterium bovis BCG Reviewed

    Makiko Yamashita, Shoutaro Tsuji, Akihito Nishiyama, Quentin N. Myrvik, Ruth Ann Henriksen, Yoshimi Shibata

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   293 ( 1 )   C184 - C190   2007.7

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    DOI： 10.1152/ajpcell.00346.2006

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  • Immunologic response enhances atherosclerosis - type 1 helper T cell (Th1)-to-type 2 helper T cell (Th2) shift and calcified atherosclerosis in bacillus Calmette-Guerin (BCG)-treated apolipoprotein E-knockout (apo E-/-) mice Reviewed

    Yoshimi Shibata, Hiroyoshi Ohata, Makiko Yamashita, Shoutaro Tsuji, John F. Bradfield, Akihito Nishiyama, Ruth Ann Henriksen, Quentin N. Myrvik

    TRANSLATIONAL RESEARCH   149 ( 2 )   62 - 69   2007.2

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    DOI： 10.1016/j.trsl.2006.08.008

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  • Heat-killed BCG induces biphasic cyclooxygenase 2(+) splenic macrophage formation - role of IL-10 and bone marrow precursors Reviewed

    Yoshimi Shibata, Jon Gabbard, Makiko Yamashita, Shoutaro Tsuji, Mike Smith, Akihito Nishiyama, Ruth Ann Henriksen, Quentin N. Myrvik

    JOURNAL OF LEUKOCYTE BIOLOGY   80 ( 3 )   590 - 598   2006.9

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    DOI： 10.1189/jlb.1205737

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  • Assembly of staphylococcal leukocidin into a pore-forming oligomer on detergent-resistant membrane microdomains, lipid rafts, in human polymorphonuclear leukocytes Reviewed

    Akihito Nishiyama, Jun Kaneko, Masahiko Harata, Yoshiyuki Kamio

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   70 ( 6 )   1300 - 1307   2006.6

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    DOI： 10.1271/bbb.50499

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  • Phagocytosis of N-acetyl-D-glucosamine particles, a Th1 adjuvant, by RAW 264.7 cells results in MAPK activation and TNF-alpha, but not IL-10, production Reviewed

    Akihito Nishiyama, Shoutaro Tsuji, Makiko Yamashita, Ruth Ann Henriksen, Quentin N. Myrvik, Yoshimi Shibata

    CELLULAR IMMUNOLOGY   239 ( 2 )   103 - 112   2006.2

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    DOI： 10.1016/j.cellimm.2006.04.003

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  • Differential effects of IL-10 on prostaglandin H synthase-2 expression and prostaglandin E-2 biosynthesis between spleen and bone marrow macrophages Reviewed

    Y Shibata, A Nishiyama, H Ohata, J Gabbard, QN Myrvik, RA Henriksen

    JOURNAL OF LEUKOCYTE BIOLOGY   77 ( 4 )   544 - 551   2005.4

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    DOI： 10.1189/jlb.0504311

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  • Identification of serine138 residue in the 4-residue segment K135K136I137S138 of LukS-I component of Staphylococcus intermedius leukocidin crucial for the LukS-I-specific function of staphylococcal leukocidin Reviewed

    A Nishiyama, MARV Guerra, N Sugawara, K Yokota, J Kaneko, Y Kamio

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   66 ( 2 )   328 - 335   2002.2

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    DOI： 10.1271/bbb.66.328

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  • Phosphorylation of LukS by protein kinase A is crucial for the LukS-specific function of the staphylococcal leukocidin on human polymorphonuclear leukocytes Reviewed

    A Nishiyama, H Nariya, Y Kamio

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   62 ( 9 )   1834 - 1838   1998.9

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    DOI： 10.1271/bbb.62.1834

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  • Identification of the minimum segment in which the threonine(246) residue is a potential phosphorylated site by protein kinase A for the LukS-specific function of staphylococcal leukocidin Reviewed

    H Nariya, A Nishiyama, Y Kamio

    FEBS LETTERS   415 ( 1 )   96 - 100   1997.9

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    DOI： 10.1016/S0014-5793(97)01100-9

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▶ display all

Books

  • BCG 2nd Edition -TB vaccine- Application against tuberculosis and other diseases

    Akihito Nishiyama, Sohkichi Matsumoto（ Role： Joint author ,  Chapter 14. Bacterial factors regulating M. tuberculosis infection and persistence）

    Japan Anti-Tuberculosis Association (JATA)  2022 

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    Responsible for pages：212-234   Language：English Book type：Scholarly book

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  • 病原微生物学 基礎と臨床

    荒川宜親, 神谷茂, 柳雄介 編（ Role： Joint author ,  3.3 抗酸菌と放線菌（西山晃史、松本壮吉 著））

    東京化学同人  2014 

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    Responsible for pages：120-130   Language：Japanese Book type：Scholarly book

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  • 病原菌の今日的意味 改訂4版

    松本慶蔵（ Role： Joint author ,  下痢性大腸菌（diarrheagenic E. coli）（山本達男、西山晃史、高野智洋 著））

    医薬ジャーナル社  2011 

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    Responsible for pages：445 – 472   Language：Japanese Book type：Scholarly book

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  • MRSA –基礎・臨床・対策-

    河野茂 編（ Role： Joint author ,  市中感染型MRSA（山本達男、西山晃史、高野智洋、樋口渉 著））

    医薬ジャーナル社  2010 

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    Responsible for pages：202-212   Language：Japanese Book type：Scholarly book

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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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • Electron Microscopic Study of H. pylori Infection (Particularly Protein - losing Gastropathy)

    127 ( 2 )   71 - 76   2013.2

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  • Additional Information on Emerging Multiple Drug-resistant Gram-negative rods : Bacterial Characteristics of NDM-1-producing Escherichia coli (Infectious Mechanisms) (Metallo-β-lactamases and Multiple Drug-resistant Gram-negative Bacterial Infections)

    Yamamoto Tatsuo, Takano Tomomi, Iwao Yasuhisa, Higuchi Wataru, Nishiyama Akihito

    126 ( 8 )   410 - 413   2012.8

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  • Summer Student Visit Program to Russia: Five Years after Restart and 2010 (New Friendship, Raising the Level, and Niigata to Russia)

    Reva Ivan, Nozaki Asami, Endo Yuka, Matsuo Ryoko, Mitsuishi Atsuyuki, Tsukamoto Kenji, Reva Ivan, Takano Tomomi, Iwao Yasuhisa, Higuchi Wataru, Nishiyama Akihito, Yamamoto Tatsuo

    125 ( 12 )   686 - 690   2011.12

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  • Kidney transplantation Q & A

    Kiselev Ilia, Protopopova Elena, Shermatova Ksenia, Reva Ivan, Razvina Olga, Kiselev Ilia, Protopopova Elena, Shermatova Ksenia, Saito Kazuhide, Takahashi Kota, Iwao Yasuhisa, Higuchi Wataru, Reva Ivan, Razvina Olga, Takano Tomomi, Nishiyama Akihito, Yamamoto Tatsuo

    125 ( 10 )   571 - 574   2011.10

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  • Pediatric leukemia, Parkinson's disease, and cancer operations in Russia and Japan

    Podkaura Oxana, Gavrikova Valeria, Korneev Stanislav, Razvina Olga, Reva Ivan, Podkaura Oxana, Gavrikova Valeria, Korneev Stanislav, Imai Chihaya, Uchiyama Makoto, Murakami Hiroatsu, Masuda Hiroshi, Kuroha Yasuko, Koike Ryoko, Uchiyama Seiji, Kosugi Shinichi, Hatakeyama Katsuyoshi, Razvina Olga, Reva Ivan, Takano Tomomi, Nishiyama Akihito, Yamamoto Tatsuo

    124 ( 4 )   228 - 234   2010.4

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  • 感染制御のための微生物学講座 細菌 ブドウ球菌毒素

    西山 晃史, 高野 智洋, 樋口 渉

    感染制御   6 ( 1 )   33 - 38   2010.2

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  • 6 ホスホマイシンの新しい作用の探索(I.一般演題,第47回新潟化学療法研究会)

    西山 晃史, 近 幸吉, 田邊 嘉也, 下条 文武, 山本 達男

    新潟医学会雑誌   123 ( 6 )   323 - 323   2009.6

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  • 5 ヒト免疫細胞に対するホスホマイシンの作用(I.一般演題,第46回新潟化学療法研究会)

    大久保 猛司, 近 幸吉, 西山 晃史, 田邊 嘉也, 下条 文武, 山本 達男

    新潟医学会雑誌   123 ( 6 )   319 - 320   2009.6

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  • Characterization of the cagA gene EPIYA motif of Helicobacter pylori from Russia

    Makhinov Konstantin, Iwan Reva, Higuchi Wataru, Takano Tomomi, Nishiyama Akihito, Yamamoto Tatsuo

    122 ( 10 )   585 - 588   2008.10

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  • Catalytically inactive cyclooxygenase 2 (COX-2) and absence of PGE2 biosynthesis in murine peritoneal macrophages following in vivo phagocytosis of heat-killed Mycobacterium bovis BCG

    Yoshimi Shibata, Tsutomu Shinohara, Shoutaro Tsuji, Ruth Ann Henriksen, Akihito Nishiyama, Quentin N. Myrvik, Makiko Yamashita

    JOURNAL OF IMMUNOLOGY   178   2007.4

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  • Differential regulation of cyclooxygenase (COX) isoforms in alveolar (AM) and peritoneal macrophages (PM) from heat-killed Mycobacterium bovis BCG treated mice

    Tsutomu Shinohara, Makiko Yamashita, Akihito Nishiyama, Shoutaro Tsuji, Ruth Ann Henriksen, Quentin N. Myrvik

    JOURNAL OF IMMUNOLOGY   178   2007.4

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  • The effect of cellular cholesterol depletion on marine macrophage activation induced by phagocytosis of chitin

    Akihito Nishiyama, Shoutaro Tsuji, Makiko Yamashita Tsuji, Ruth Ann Henriksen, Quentin N. Myrvik, Yoshimi Shibata

    JOURNAL OF IMMUNOLOGY   176   S178 - S178   2006.4

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  • Mechanism of BCG-induced high anti-HSP65 antibody formation and development of advanced atherosclerosis in apolipoprotein E-/-mice

    Yoshimi Shibata, Hiroyoshi Ohata, Makiko Yamashita Tsuji, Shoutaro Tsuji, Ruth Ann Henriksen, Akihito Nishiyama, Quentin N. Myrvik

    JOURNAL OF IMMUNOLOGY   176   S134 - S135   2006.4

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  • Molecular structure of human and mouse interlectin-1 and comparison of binding to a mycobacterial galactofuranosyl residue

    Shoutaro Tsuji, Makiko Yamashita Tsuji, Akihito Nishiyama, Yoshimi Shibata

    JOURNAL OF IMMUNOLOGY   176   S87 - S87   2006.4

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  • Heat-killed BCG induces biphasic cyclooxygenase-2 (COX-2) splenic macrophage formation - differential intracellular compartmentalization of COX-2 correlates with PGE(2) biosynthesis

    Makiko Yamashita Tsuji, Shoutaro Tsuji, Akihito Nishiyama, Ruth Ann Henriksen, Quentin N. Myrvik, Yoshimi Shibata

    JOURNAL OF IMMUNOLOGY   176   S6 - S6   2006.4

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  • N-acetyl-beta-D-glucosamine polymer particle-induced Th1 and Th2 cytokine production by murine macrophage-like RAW264.7 cells are differentially regulated by p38, JNK, and Erk 1/2

    A Nishiyama, J Gabbard, H Ohara, RA Henriksen, QN Myrvik, Y Shibata

    FASEB JOURNAL   19 ( 4 )   A374 - A374   2005.3

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  • Biphasic expression of Cox-2 by splenic macrophages (MO) in BCG-immunized mice

    Y Shibata, H Ohata, A Nishiyama, J Gabbard, QN Myrvik, RA Henriksen

    FASEB JOURNAL   19 ( 4 )   A964 - A964   2005.3

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  • Mycobacteria-induced osteoclastogenesis and PGE(2)-releasing macrophage formation in the mouse spleen

    H Ohata, A Nishiyama, RA Henriksen, QN Myrvik, Y Shibata

    FASEB JOURNAL   18 ( 4 )   A625 - A625   2004.3

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  • Mechanism of phagocytosed particle-induced IL-12 production in macrophage

    A Nishiyama, H Ohata, RA Henriksen, QN Myrvik, Y Shibata

    FASEB JOURNAL   18 ( 5 )   A1026 - A1026   2004.3

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  • Marrow-derived splenic macrophages expressing Cox-2 may contribute to increased PGE(2) production in BCG-immunized mice

    Y Shibata, M Smith, QN Myrvik, H Ohata, A Nishiyama, RA Henriksen

    FASEB JOURNAL   18 ( 4 )   A460 - A460   2004.3

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Presentations

  • Dynamic action of an intrinsically disordered histone-like protein in DNA compaction that induces mycobacterial dormancy

    Akihito Nishiyama, Masahiro Shimizu, Tomoyuki Narita, Noriyuki Kodera, Ozeki Yuriko, Kouta Mayanagi, Takehiro Yamaguchi, Yoshitaka Tateishi, Sohkichi Matsumoto

    The U.S.-Japan Cooperative Medical Sciences Program: Mycobacterial Diseases Panel Meeting 2024  2024.4 

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    Event date： 2024.4

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

    Geberetsadik G, Inaizumi A, Nishiyama A, Yamaguchi T, Hamamoto H, Panthee S, Tamaru A, Mizutani Y, Kaboso SA, Hakamata M, Ilinov A, Ozeki Y, Tateishi Y, Sekimizu K, Matsumoto S

    The 15th Korea-Japan International Symposium on Microbiology  2022.10 

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  • Dynamic action of an intrinsically disordered protein in DNA compaction that induces mycobacterial dormancy Invited

    Akihito Nishiyama, Masahiro Shimizu, Tomoyuki Narita, Noriyuki Kodera, Yuriko Ozeki, Akira Yokoyama, Kouta Mayanagi, Takehiro Yamaguchi, Yoshitaka Tateishi, Sohkichi Matsumoto

    The 15th Korea-Japan International Symposium on Microbiology  2022.10 

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    Event date： 2022.10

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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  2024.5 

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  • 抗酸菌の天然変性ヒストン様タンパク質 -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, 松本壮吉

    日本生物物理学会第61回年会  2023.11 

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  • 抗酸菌の休眠誘導に関わる天然変性ヒストン様タンパク質によるDNA凝集の動的メカニズムの解析

    西山晃史, 清水将裕, 成田知恕, 古寺哲幸, Anna Savitskaya, 尾関百合子, 横山 晃, 真柳浩太, 山口雄大, 立石善隆, 松本壮吉

    第23回日本蛋白質学科学年会  2023.7 

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  • 抗酸菌ヒストン様タンパク質は天然変性領域を介して核酸との相分離を誘導する

    西山晃史, 目黒佳未, 真鍋陸, 加藤成祥, 尾関百合子, 立石善隆, 松本壮吉

    第96回日本細菌学会総会  2023.3 

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  • Inactivation of DNA function by intrinsically disordered histone-like protein in mycobacteria Invited

    Akihito Nishiyama, Masahiro Shimizu, Noriyuki Kodera, Anna Savitskaya, Yuriko Ozeki, Kouta Mayanagi, Takehiro Yamaguchi, Yoshitaka Tateishi, Sohkichi Matsumoto

    2022.3 

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  • 抗酸菌ヒストン様蛋白質による天然変性領域を介した新規のDNA凝集メカニズム

    西山晃史, 清水将裕, 成田知恕, 古寺哲幸, 尾関百合子, 横山 晃, 真柳浩太, 山口雄大, 袴田真理子, 立石善隆, 松本壮吉

    第58回日本細菌学会中部支部総会  2021.11 

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  • Mycobacterial DNA-binding protein 1, a major protein in hypoxic dormant mycobacteria

    Akihito Nishiyama, Noriyuki Kodera, Masahiro Shimizu, Anna Savitskaya, Shymaa Enany, Kouta Mayanagi, Takehiro Yamaguchi, Yoshitaka Tateishi, Sohkichi Matsumoto

    2021.3 

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  • Adduct formation of delamanid with NAD in mycobacteria

    Akihito Nishiyama, Mikayo Hayashi, Ryuki Kitamoto, Yoshitaka Tateishi, Mayuko Osada-Oka, Yukiko Nishiuchi, Xiuhao Chen, Kentaro Kaneko, Makoto Matsumoto, Sohkichi Matsumoto

    2021.3 

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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

    第93回日本細菌学会総会  2020.2 

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  • The functions of mycobacterial histone-like protein MDP1, a major protein in dormant mycobacteria Invited

    Akihito Nishiyama, Anna Savitskaya, Shymaa Enany, Takehiro Yamaguchi, Naoya Ohara, Tomoyuki Narita, Noriyuki Kodera, Yuriko Ozeki, Yoshitaka Tateishi, Sohkichi Matsumoto

    2019.4 

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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, 真嶋 司, 有坂文雄, 津中康央, 藤原芳江, 西山晃史, 吉田 豊, 北所健悟, 小林 悠, 金子幸弘, 中川一路, 前倉亮治, 山本三郎, 片平正人, 松本壮吉

    第55回日本細菌学会中部支部総会  2018.10 

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  • 抗酸菌ヒストン様タンパク質による染色体制御における天然変性領域の役割

    西山晃史, Anna Savitskaya, 山口雄大, 大原直也, 尾関百合子, 立石善隆, 松本壮吉

    第55回日本細菌学会中部支部総会  2018.10 

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

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

    The 52nd US-Japan Mycobacteria Panel Meeting  2018.3 

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  • Conditional control of mycobacterial DNA-binding protein 1 expression in mycobacteria

    Anna Savitskaya, 西山晃史, 松本壮吉

    第91回日本細菌学会総会  2018.3 

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  • The analysis of mycobacterial DNA-binding protein 1 function in mycobacteria using conditional expression system

    Anna Savitskaya, 西山晃史, 松本壮吉

    第2回抗酸菌研究会  2017.10 

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  • 抗酸菌の長期生存とヒストン様核様体結合タンパク質によるグローバルな細胞機能制御

    西山晃史, Shymaa Enany、Anna Savitskaya, 吉田 豊, 山本 格, 阿戸 学, 松本壮吉

    第54回日本細菌学会中部支部総会  2017.10 

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  • Conditional expression of mycobacterial DNA-binding protein 1 function in mycobacteria

    Anna Savitskaya, Akihito Nishiyama, Naoya Ohara, Sohkichi Matsumoto

    2017.3 

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  • Histone-like protein-dependent control of mycobacterial functions critical for long-term survival

    Akihito Nishiyama, Shymaa Enany, Yoshitaka Tateishi, Yuriko Ozeki, Anna Savitskaya, Takehiro Yamaguchi, Yukiko Nishida, Manabu Ato, Sohkichi Matsumoto

    第90回日本細菌学会総会  2017.3 

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  • 抗酸菌の遅延発育、長期生存及び薬剤抵抗性におけるヒストン様タンパク質の役割

    西山晃史, Shymaa Enany、Anna Savitskaya, 吉田 豊, 立石善隆, 尾関百合子, 山口雄大, 西田由貴子, 山本 格, 大原直也, 阿戸 学, 松本壮吉

    日米医学協力計画 抗酸菌症部会国内会議  2017.1 

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  • The crucial role of the C-terminal region of mycobacterial DNA-binding protein 1 in DNA compaction, growth suppression, and drug tolerance

    Anna Savitskaya, Akihito Nishiyama, Sohkichi Matsumoto

    第１回抗酸菌研究会  2016.9 

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  • ヒストン様DNA結合タンパク質による結核菌の増殖抑制作用

    西山晃史, Anna Savitskaya, 松本壮吉

    第10回細菌学若手コロッセウム  2016.7 

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Research Projects

  • 結核菌天然変性蛋白質-核酸凝集の分子機序の解明と核酸医薬への応用

    Grant number：24K10216

    2024.4 - 2027.3

    System name：科学研究費助成事業

    Research category：基盤研究(C)

    Awarding organization：日本学術振興会

    西山 晃史

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    Authorship：Principal investigator 

    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

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  • 天然変性蛋白質(IDP)を標的とする、中分子化合物による、新しい創薬フィールドの開拓

    Grant number：22gm1610009h0001

    2022.10 - 2028.3

    System name：革新的先端研究開発支援事業

    Research category：ユニットタイプ「AMED-CREST」研究開発領域

    Awarding organization：国立研究開発法人日本医療研究開発機構AMED

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  • 結核の発病予測向上と治療期間 短縮を目指した生物学的要因の 探索（研究分担者）

    2019.4 - 2022.3

    System name：感染症実用化 研究事業・新 興・再興感染 症に対する革 新的医薬品等 開発推進研究 事業

    Awarding organization：AMED

    慶長直人

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  • 細菌における天然変性蛋白質のヒストンコード機構による形質制御の証明

    2017.4 - 2020.3

    System name：科学研究費補助金（基盤C一般・代表）

    Awarding organization：日本学術振興会

    西山晃史

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    Authorship：Principal investigator  Grant type：Competitive

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  • 結核菌の潜在化機構の解析と、潜在化の維持による結核制圧戦略の構築

    2016.4 - 2019.3

    System name：科学研究費補助金(基盤B一般・分担）

    Awarding organization：日本学術振興会

    松本壮吉

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    Grant type：Competitive

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  • 結核菌抗原による形質細胞様樹状細胞の活性化を介する新しい結核防御免疫機構の解明

    2015.4 - 2018.3

    System name：科学研究費補助金（基盤C一般・分担）

    Awarding organization：日本学術振興会

    鈴木史子

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    Grant type：Competitive

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  • Investigation of the cytolytic mechanisms of Panton-Valentine leukocidin

    Grant number：20790331

    2008.4 - 2010.3

    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

    NISHIYAMA Akihito

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    Authorship：Principal investigator  Grant type：Competitive

    Panton-Valentine leukocidin (PVL) is a virulence factor of community-acquired methicillin-resistant Staphylococcus aureus. We have demonstrated the lipid raft-mediated pore formation of PVL. Since integrity of lipid rafts did not affect on the recognition of target cells by PVL, novel PVL receptor(s), other than ganglioside GM1, is suggested. This receptor molecule may be a possible target of PVL inhibitor.

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  • 黄色ブドウ球菌の産生するロイコシジンのヒト好中球崩壊機構の解明

    Grant number：00J06222

    2000 - 2002

    System name：科学研究費助成事業

    Research category：特別研究員奨励費

    Awarding organization：日本学術振興会

    西山 晃史

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    Grant amount：\3000000 （ Direct Cost: \3000000 ）

    黄色ブドウ球菌の産生する白血球崩壊毒素ロイコシジン(Luk)はLukS、LukFからなり、ヒト及びウサギ白血球を特異的に崩壊する。崩壊活性の発現にはLukSのリン酸化、及び両成分による膜孔形成が必須である。本研究はLukの白血球崩壊機構の全容を解明することを目的とする。そこで最終年度である本年度は以下のことを行った。
    1.LukS reseptorのスクリーニング
    前年度までに酵母を用いたtwo-hybrid systemにおいてLukSのリン酸化部位を含むC末端領域をプローブとして、このLukSに結合性を示すクローンをヒト末梢血白血球cDNA libraryからスクリーニングした結果、toll-like receptor 4の細胞外ドメインに結合する膜表層タンパク質MD-2を取得した。MD-2をコードするcDNAをpET-22b(+)にクローニングし、大腸菌を形質転換し、C末端にHis-tagを付加させたMD-2(MD-2-6His)を発現させた。現在、MD-2-6Hisを精製し、LukSとのin vitroでの結合を検討中である。
    2.Lukのヒト白血球崩壊活性に対するraftの関与の検討
    LukSのヒト白血球の認識にGM1が関与すること、及び白血球に結合したLukSが非イオン性界面活性剤によって可溶化されないことから、Lukのヒト白血球崩壊活性に細胞膜マイクロドメインraftが関与していることが示唆された。そこで、raftを崩壊させるmethyl-β-cyclodextrin(MBCD)の効果を検討したところ、MBCDによってLukの活性が阻害された。また、毒素処理したヒト白血球をBrij 35で可溶化した後、lysateをショ糖密度勾配法で分画した結果、毒素成分がraftの含まれる画分に分画された。以上の結果、Lukのヒト白血球崩壊活性にraftが関与している可能性が強く示唆された。

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Teaching Experience (researchmap)

  • 微生物学

    2020.7
    Institution name：新潟県立十日町看護専門学校

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  • 感染と免疫（細菌学総論）

    Institution name：新潟大学大学院医歯学総合研究科医学科専攻（修士課程）

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  • 生体防御と感染（細菌学）

    Institution name：新潟大学医学部医学科

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Teaching Experience

  • 感染と免疫

    2014.5
    -
    2023
    Institution name：新潟大学

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    Level：Postgraduate 

  • 生体防御と感染(細菌学)

    2013
    Institution name：新潟大学