記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   出版者・発行元：日本細菌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：日本語   出版者・発行元：(一社)日本結核・非結核性抗酸菌症学会  

[目的]全ゲノム解析を用いて,早期発症者と長期潜伏後発症者から分離した結核菌北京株のゲノム変異を解析した。[方法]1999年に中学校で発生した結核集団感染の接触者と二次感染者のうち2009年までに結核を発症した患者より分離した結核菌北京株6株と,別の事例で初発時と再発時の患者より分離した結核菌北京株2株の計8株の全ゲノム解析を行った。結核菌の突然変異率は,初発から1年以内に発症した早期発症者と1年以上の潜伏期を経てから発症または再燃した長期潜伏後発症者の2群間で比較した。[結果]結核菌北京株の突然変異率は,Lineage 4に属する結核菌よりも高く,結核菌北京株の高い病原性や薬剤耐性の要因である可能性が示唆された。遺伝子多型解析では,酸化的損傷に起因すると推定されている突然変異が長期潜伏後発症群のほうに多く,潜伏期間中にも薬剤耐性変異が起こる可能性が示唆された。[結論]結核菌北京株の高頻度の薬剤耐性化を防ぐためには,感染した結核菌の系統により治療法を検討する必要性も考えられた。今後,結核菌系統の特性を理解し,治療法を工夫することで結核の薬剤耐性化や重篤化を防ぐ有効な対策の構築につながることが期待される。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Mycobacterium intracellulare is a representative etiological agent of emerging pulmonary M. avium-intracellulare complex disease in the industrialized countries worldwide. The recent genome sequencing of clinical strains isolated from pulmonary M. avium-intracellulare complex disease has provided insight into the genomic characteristics of pathogenic mycobacteria, especially for M. avium; however, the genomic characteristics of M. intracellulare remain to be elucidated. RESULTS: In this study, we performed comparative genomic analysis of 55 M. intracellulare and related strains such as M. paraintracellulare (MP), M. indicus pranii (MIP) and M. yonogonense. Based on the average nucleotide identity, the clinical M. intracellulare strains were phylogenetically grouped in two clusters: (1) the typical M. intracellulare (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., fadE3, fadE33), transporters (e.g., mce3), and type VII secretion system (genes of ESX-2 system) were shown to be hypermutated in the clinical strains. M. intracellulare was shown to be pan-genomic at the species and subspecies levels. The mce genes were specific to particular subspecies, suggesting that these genes may be helpful in discriminating virulence phenotypes between subspecies. CONCLUSIONS: Our data suggest that genomic diversity among M. intracellulare, M. paraintracellulare, M. indicus pranii and M. yonogonense remains at the subspecies or genovar levels and does not reach the species level. Genetic components such as mce genes revealed by the comparative genomic analysis could be the novel focus for further insight into the mechanism of human pathogenesis for M. intracellulare and related strains.

DOI： 10.1186/s12866-021-02163-9

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：英語  

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

DOI： 10.1371/journal.pone.0256946

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

<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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その他リンク： http://www.nature.com/articles/s41598-020-62287-2

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Mycobacterium tuberculosis (Mtb) 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 Mtb 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 Mtb are exposed to oxidative stress in the latent state. Our data thus demonstrates that higher mutation rates of Mtb 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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記述言語：日本語   出版者・発行元：(一社)日本結核・非結核性抗酸菌症学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：American Society for Microbiology  

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
₄₂₀
)-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.

DOI： 10.1128/aac.01755-19

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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 (F420)-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 Mycobacterium tuberculosis var. Bacille de Calmette et Guérin. Isoniazid-resistant mutations in the type II NADH dehydrogenase gene (ndh) showed a higher intracellular NADH/NAD ratio and cross-resistance to DLM, which were restored by complementation of the mutants with wild-type ndh 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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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：英語   出版者・発行元：日本細菌学会  

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記述言語：英語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：日本細菌学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.bjid.2019.07.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/intimm/dxz048

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DOI： 10.1111/1348-0421.12674

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41598-018-26463-9

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DOI： 10.1371/journal.pone.0204160

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Bacteria can proliferate perpetually without ageing, but they also face conditions where they must persist. Mycobacteria can survive for a long period. This state appears during mycobacterial diseases such as tuberculosis and leprosy, which are chronic and develop after long-term persistent infections. However, the fundamental mechanisms of the long-term living of mycobacteria are unknown. Every Mycobacterium species expresses Mycobacterial DNA-binding protein 1 (MDP1), a histone-like nucleoid associated protein. Mycobacterium smegmatis is a saprophytic fast grower and used as a model of mycobacterial persistence, since it shares the characteristics of the long-term survival observed in pathogenic mycobacteria. Here we show that MDP1-deficient M. smegmatis dies more rapidly than the parental strain after entering stationary phase. Proteomic analyses revealed 21 upregulated proteins with more than 3-fold in MDP1-deficient strain, including DnaA, a replication initiator, NDH, a NADH dehydrogenase that catalyzes downhill electron transfer, Fas1, a critical fatty acid synthase, and antioxidants such as AhpC and KatG. Biochemical analyses showed elevated levels of DNA and ATP syntheses, a decreased NADH/NAD(+) ratio, and a loss of resistance to oxidative stress in the MDP1-knockout strain. This study suggests the importance of MDP1-dependent simultaneous control of the cellular functions in the long-term survival of mycobacteria.

DOI： 10.1038/s41598-017-06480-w

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Mycobacterium avium subsp. hominissuis (MAH) is the major causative agent of nontuberculous mycobacteriosis, the representative case of environment-related infectious diseases the incidence of which is increasing in industrialized countries. MAH is found in biofilm in drinking water distribution system and residential environments. We investigated the effect of gaseous and nutritional conditions, and the role of glycopeptidolipids (GPLs) on biofilm-like pellicle formation in MAH. Pellicle formation was observed under 5% oxygen in Middlebrook 7H9 broth containing 0.2% glycerol and 10% albumindextrose- catalase enrichment but not under normoxia or in nutrient- poor media. An analysis of 17 environmental isolates revealed that hypoxia (5% oxygen) preferentially enhanced pellicle formation both in plastic plates and in glass tubes, compared with hypercapnia (5% carbon dioxide). Wild-type strains (WT) developed much thicker pellicles than GPL-deficient rough mutants (RM). WT bacterial cells distributed randomly and individually in contrast to that RM cells positioned linearly in a definite order. Exogenous supplementation of GPLs thickened the pellicles of RM, resulting in a similar morphological pattern to WT. These data suggest a significant implication of eutrophication and hypoxia in biofilm-like pellicle formation, and a functional role of GPLs on development of pellicles in MAH.

DOI： 10.1038/srep41775

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0141658

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INFORMA HEALTHCARE  

The survival rate of chronic obstructive pulmonary disease (COPD) patients with severely reduced exercise capacity is extremely low. We recently identified three life-threatening pathophysiological conditions during cardiopulmonary exercise testing (CPET): (1) exercise-induced hypoxemia, (2) sympathetic overactivity, and (3) progressive respiratory acidosis at low-intensity exercise. The present prospective observation study aimed to determine whether these parameters constitute risk factors of mortality in moderate-to-very severe COPD. Ninety-six COPD patients were followed-up, monthly, for &gt; 3 years. Subsequently, spirometry and CPET were performed to examine parameters of exercise-induced hypoxemia ([PaO2 slope, mmHg/L.min(-1)] = Decrease in PaO2/Delta VO2 (Difference in Delta VO2 between at rest and at peak exercise)), progression of acidosis ([Delta pH/Delta VO2/L.min(-1)] = Decrease in pH/Delta VO2), and sympathetic overactivity ([Delta norepinephrine(NE)/Delta VO2, ng/mL/L.min(-1)] = increase in NE/Delta VO2). Univariate analysis revealed a significant association between the three conditions with increased mortality. Kaplan-Meier analysis showed that the quartile combining the steepest PaO2 slope (&lt;=-55 mmHg/Delta VO2 [L/min]), steepest decrease in arterial blood pH (&lt;= -1.72/Delta VO2 [L/min]), and most rapid increase in plasma NE level (&gt;= 5.2 ng/Delta VO2 [L/min]) during incremental exercise was associated with higher all-cause mortality. These conditions showed cumulative effects on COPD patients' survival. Multivariate analyses revealed that these three life-threatening factors are also independent predictors of mortality based on age, heart rate and PaO2 at rest, body mass index, and forced expiratory volume in 1 s. Thus, these new exercise-induced mortality risk factors may lead to more efficient pulmonary rehabilitation programs for COPD patients based on patient-specific exercise-induced pathophysiological profiles.

DOI： 10.3109/15412555.2014.898038

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1128/genomeA.01062-14

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：DAEDALUS ENTERPRISES INC  

BACKGROUND: Patients with COPD have reduced exercise tolerance associated with dyspnea. This exercise intolerance is primarily due to impaired ventilatory mechanics, but it is also associated with a combination of factors, including inefficient gas exchange, lactic acidosis at a low work rate, and exercise-induced hypoxemia. The survival prognosis of COPD patients with severely reduced exercise capacity is extremely poor, but the pathophysiology of these patients during exercise remains to be accurately established. The present study aimed to characterize life-threatening factors such as hypoxemia, acidosis, and sympathetic activation during exercise in these patients. METHODS: We monitored changes in life-threatening factors and compared these factors among quartile groups, defined according to their peak oxygen uptake status. Ninety-one COPD subjects (82 males, 9 females, average age 69.7 +/- 6.8 y) consecutively underwent incremental cardiopulmonary exercise testing using a cycle ergometer. Arterial blood gases, lactate, and catecholamines were measured during cardiopulmonary exercise testing. RESULTS: The pathophysiology of the COPD differed among the 4 subject groups. Subjects with the most severely reduced exercise capacity (peak oxygen uptake &lt;= 623 mL/min) were characterized by exercise-induced steep decrease in P-aO2 slope (-78 +/- 70 mm Hg/L/min), rapid progression of respiratory acidosis, little change in lactic acidosis, and sympathetic activation at low-intensity work load (plasma norepinephrine 1.41 +/- 0.94 ng/mL at 20 watts work load), in addition to the limitation of increase in ventilation and impaired gas exchange. CONCLUSIONS: The mechanisms of exercise intolerance in COPD patients significantly differed among subjects with different exercise capacities. Subjects with the most severely reduced exercise capacity had the characteristics of exercise-induced hypoxemia, sympathetic overactivity, and progressive respiratory acidosis at low-intensity exercise. These life-threatening pathophysiological conditions could be improved by medication and/or pulmonary rehabilitation.

DOI： 10.4187/respcare.02201

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：IWA PUBLISHING  

We previously demonstrated the colonization of Mycobacterium avium complex in bathrooms by the conventional culture method. In the present study, we aimed to directly detect M. avium organisms in the environment using loop-mediated isothermal amplification (LAMP), and to demonstrate the efficacy of LAMP by comparing the results with those obtained by culture. Our data showed that LAMP analysis has detection limits of 100 fg DNA/reaction for M. avium. Using an FTA (R) elute card,DNA templates were extracted from environmental samples from bathrooms in the residences of 29 patients with pulmonary M. avium disease. Of the 162 environmental samples examined, 143 (88%) showed identical results by both methods; 20 (12%) and 123 (76%) samples were positive and negative, respectively, for M. avium. Of the remaining 19 samples (12%), seven (5%) and 12 (7%) samples were positive by the LAMP and culture methods, respectively. All samples that contained over 20 colony forming units/primary isolation plate, as measured by the culture method, were also positive by the LAMP method. Our data demonstrate that the combination of the FTA elute card and LAMP can facilitate prompt detection of M. avium in the environment.

DOI： 10.2166/wh.2013.007

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: The aim of this substudy of the ghrelin treatment, multicenter, randomized, double-blind, placebo-controlled trial was to investigate the effects of ghrelin administration on exercise capacity and the underlying mechanisms in underweight patients with chronic obstructive pulmonary disease (COPD) using cardiopulmonary exercise testing.
Methods: Twenty underweight COPD patients were randomized to pulmonary rehabilitation with intravenous ghrelin (2 mu g/kg, n = 10) or placebo (n = 10) twice daily for 3 weeks in a double-blind fashion. The primary outcome was changes in peak oxygen uptake ((V) over dot O-2). Secondary outcomes included changes in exertional cardio-respiratory functions: O-2-pulse, physiologic dead space/tidal volume-ratio (V-D/V-T), ventilatory equivalent for oxygen ((V) over dot(E)/(V) over dotO(2)), and ventilatory equivalent for carbon dioxide ((V) over dot(E)//(V) over dotCO(2)).
Results: With incremental exercise, at peak exercise, there was a significant difference in the mean difference (ghrelin minus placebo), i.e., treatment effect in: i) peak (V) over dotO(2) (1.2 mL/kg/min, 95% CI: 0.2-2.3 mL/kg/min, between-group p = 0.025); ii) (V) over dot(E)/(V) over dotO(2) (-4.2, 95% CI: -7.9 to -0.5, between-group p = 0.030); iii) (V) over dot(E)/(V) over dotCO(2) (-4.1, 95% CI: -8.2 to -0.1, between-group p = 0.045); iv) V-D/V-T (-0.04, 95% CI: -0.08 to -0.00, between-group p = 0.041); and v) O-2-pulse (0.7 mL/beat, 95% CI: 0.3 to 1.2 mL/beat, between-group p = 0.003). Additionally, repeated-measures analysis of variance (ANOVA) indicated a significant time-course effect of ghrelin versus placebo in the peak (V) over dotO(2) (p = 0.025).
Conclusion: Ghrelin administration was associated with improved exertional capacity and improvements in ventilatory-cardiac parameters.

DOI： 10.1186/1471-2466-13-37

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

To understand the mechanism of exertional dyspnea, we postulated that, despite hyperoxia during exercise, patients with idiopathic pulmonary fibrosis (IPF) might not regulate exertional acidosis by ventilatory compensation to stop exercise. The exercise responses during 30% O(2) or compressed air (CA) were examined in 13 patients with IPF. The PaO(2), PaCO(2), and HCO(3)(-) levels were higher during exercise with hyperoxia than with CA. At peak exercise, hyperoxia reduced the plasma lactate level. The dyspnea-ratio (%) of the ΔV(O(2)) (peak minus resting oxygen uptake) curve reached a break point that occurred at a similar exercise point with hyperoxia and CA, preceded by a break point in the breathing frequency-ratio of the ΔV(O(2)). Accordingly, the dyspnea score and pH each reached similar levels with hyperoxia and CA to stop exercise. Regardless of breathing CA or 30% O(2), IPF patients did not regulate exertional acidosis by ventilatory compensation to stop exercise, resulting in reaching a specific pH.

DOI： 10.1016/j.resp.2012.11.008

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

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.

DOI： 10.1111/j.1348-0421.2012.12005.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.1111/j.1348-0421.2012.12005.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：American Society for Microbiology  

We report the draft genome sequence of Mycobacterium tuberculosis Beijing strain OM-V02_005, which exhibits possible hypertransmissible characteristics among the population of patients with multidrug-resistant tuberculosis in Osaka Prefecture, the largest urban area in western Japan.

DOI： 10.1128/genomeA.00608-13

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：American Society for Microbiology  

We report the draft genome sequence of Mycobacterium tuberculosis Beijing strain OM-V02_005, which exhibits possible hypertransmissible characteristics among the population of patients with multidrug-resistant tuberculosis in Osaka Prefecture, the largest urban area in western Japan.

DOI： 10.1128/genomeA.00608-13

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC MICROBIOLOGY  

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.

DOI： 10.1128/JB.01439-12

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.1128/JB.01439-12

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Tuberculosis remains one of the most deadly infectious diseases worldwide and is a leading public health problem. Although isoniazid (INH) is a key drug for the treatment of tuberculosis, tolerance to INH necessitates prolonged treatment, which is a concern for effective tuberculosis chemotherapy. INH is a prodrug that is activated by the mycobacterial enzyme, KatG. Here, we show 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 with the wild-type strain. Expression of MDP1 was increased in the stationary phase and conferred growth phase-dependent tolerance to INH in M. smegmatis. Regulation of KatG expression is conserved between 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 suggest a mechanism by which phenotypic tolerance to INH is acquired in mycobacteria.

DOI： 10.1074/jbc.M111.333385

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although Mycobacterium avium complex pulmonary disease (MAC-PD) is a growing health problem, little is known about long-term radiographic outcome and factors for deterioration in patients with MAC-PD. METHODS: Data on patients with nodular bronchiectatic (NBE) MAC-PD who underwent regular follow-up for &gt
5 years were retrospectively reviewed. Changes in plain chest radiograph (CXR) and baseline characteristics were compared between the stable and deteriorated groups. RESULTS: Seventy-two patients were investigated, including 30 patients who were examined 10 years after the initial visit. One patient (1.4%) showed progressive or remarkably progressive disease on CXR at 1 year
this rate increased to 22.2% at 5 years and to 53.3% at 10 years. Body mass index (BMI) at the initial visit was lower in the deteriorated group than in the stable group. Cavitary disease and resistance to a macrolide were seen more frequently at the initial visit in the deteriorated group than in the stable group. CONCLUSIONS: NBE MAC-PD is a slowly but substantially progressive long-term infection (5-10 years). Our data suggest that patients with lower BMI, cavitary disease and resistance to a macrolide at initial visit are more likely to progress to deteriorating disease. © 2012 The Union.

DOI： 10.5588/ijtld.11.0534

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Background: Pulmonary cachexia is common in advanced chronic obstructive pulmonary disease (COPD), culminating in exercise intolerance and a poor prognosis. Ghrelin is a novel growth hormone (GH)-releasing peptide with GH-independent effects. The efficacy and safety of adding ghrelin to pulmonary rehabilitation (PR) in cachectic COPD patients were investigated.
Methodology/Principal Findings: In a multicenter, randomized, double-blind, placebo-controlled trial, 33 cachectic COPD patients were randomly assigned PR with intravenous ghrelin (2 mg/kg) or placebo twice daily for 3 weeks in hospital. The primary outcomes were changes in 6-min walk distance (6-MWD) and the St. George Respiratory Questionnaire (SGRQ) score. Secondary outcomes included changes in the Medical Research Council (MRC) scale, and respiratory muscle strength. At pre-treatment, serum GH levels were increased from baseline levels by a single dose of ghrelin (mean change, +46.5 ng/ml; between-group p&lt;0.0001), the effect of which continued during the 3-week treatment. In the ghrelin group, the mean change from pre-treatment in 6-MWD was improved at Week 3 (+40 m, within-group p = 0.033) and was maintained at Week 7 (+47 m, within-group p = 0.017), although the difference between ghrelin and placebo was not significant. At Week 7, the mean changes in SGRQ symptoms (between-group p = 0.026), in MRC (between-group p = 0.030), and in maximal expiratory pressure (MEP; between-group p = 0.015) were better in the ghrelin group than in the placebo group. Additionally, repeated-measures analysis of variance (ANOVA) indicated significant time course effects of ghrelin versus placebo in SGRQ symptoms (p = 0.049) and MEP (p = 0.021). Ghrelin treatment was well tolerated.
Conclusions/Significance: In cachectic COPD patients, with the safety profile, ghrelin administration provided improvements in symptoms and respiratory strength, despite the lack of a significant between-group difference in 6-MWD.

DOI： 10.1371/journal.pone.0035708

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Background and objective: The results of studies on the oxygen response in patients with COPD should provide important clues to the pathophysiology of exertional dyspnoea. We investigated the exercise responses to hyperoxia in relation to dyspnoea profile, as well as cardiopulmonary, acidotic and sympathetic parameters in 35 patients with stable COPD (mean FEV1 46% predicted).
Methods: This was a single-blind trial, in which patients breathed 24% O-2 or compressed air (CA) in random order during two incremental cycle exercise tests.
Results: PaO2 and PaCO2 were higher (P &lt; 0.0001 and P &lt; 0.05, respectively) at each exercise point while patients were breathing 24% O-2 compared with CA. At a standardized time point near peak exercise, use of O-2 resulted in reduced plasma lactate and plasma noradrenaline concentrations (P &lt; 0.01). Peak minute ventilation/indirect maximum voluntary ventilation was similar while breathing 24% O-2 and CA. At peak exercise, the dyspnoea score, pH and plasma noradrenaline concentrations were similar while breathing 24% O-2 and CA. The dyspnoea-ratio (%) of Delta oxygen uptake (peak minus resting oxygen uptake) curve reached a break point that occurred at a similar exercise point while breathing 24% O-2 or CA.
Conclusions: Regardless of whether they breathed CA or 24% O-2, patients with COPD did not develop ventilatory compensation for exertional acidosis, and the pH values measured were similar. Hyperoxia during a standardized exercise protocol did not alter the pattern of exertional dyspnoea in these patients, compared with breathing CA, although hyperoxia resulted in miscellaneous effects.

DOI： 10.1111/j.1440-1843.2011.02086.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：DOVE MEDICAL PRESS LTD  

Background: Tiotropium partially relieves exertional dyspnea and reduces the risk of congestive heart failure in chronic obstructive pulmonary disease (COPD) patients. However, its effect on the sympathetic activation response to exercise is unknown.
Aims: This study aimed to determine whether tiotropium use results in a sustained reduction in sympathetic activation during exercise.
Methods: We conducted a 12-week, open-label (treatments: tiotropium 18 mu g or oxitropium 0.2 mg x 3 mg), crossover study in 17 COPD patients. Treatment order was randomized across subjects. The subjects underwent a pulmonary function test and two modes of cardiopulmonary exercise (constant work rate and incremental exercise) testing using a cycle ergometer, with measurement of arterial catecholamines after each treatment period.
Results: Forced expiratory volume in 1 second and forced vital capacity were significantly larger in the tiotropium treatment group. In constant exercise testing, exercise endurance time was longer, with improvement in dyspnea during exercise and reduction in dynamic hyperinflation in the tiotropium treatment group. Similarly, in incremental exercise testing, exercise time, carbon dioxide production, and minute ventilation at peak exercise were significantly higher in the tiotropium treatment group. Plasma norepinephrine concentrations and dyspnea intensity were also lower during submaximal isotime exercise and throughout the incremental workload exercise in the tiotropium treatment group.
Conclusion: Tiotropium suppressed the increase of sympathetic activation during exercise at the end of the 6-week treatment, as compared with the effect of oxipropium. This effect might be attributed to improvement in lung function and exercise capacity and reduction in exertional dyspnea, which were associated with decreases in respiratory frequency and heart rate and reduced progression of arterial acidosis.

DOI： 10.2147/COPD.S28677

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We investigated the susceptibility to conventional and newer antimycobacterial agents including rifabutin (RBT) and novel fluoroquinolones (NFQs) among 48 clinical Mycobacterium avium complex (MAC) isolates from patients with sputum culture-positive MAC disease who were undergoing standard chemotherapy. RBT and NFQs were superior to conventional agents because of higher rates of susceptibility and lower minimum inhibitory concentration. NFQs showed cross-resistance among quinolones. In contrast, RBT did not show cross-resistance to RFP. Most clarithromycin-resistant or rifampicin-resistant cases were susceptible to RBT and NFQs. In conclusion, RBT and NFQs possess good in vitro antimicrobial activity among clinical isolates of culture-positive pulmonary MAC disease, which suggests that a combination of such microbiologically active agents may improve clinical effectiveness more than standard chemotherapy regimens.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER COLL CHEST PHYSICIANS  

DOI： 10.1378/chest.10-0248

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

The objective of this study was to investigate whether exertional dyspnea correlates with exercise responses, especially arterial blood pH and plasma norepinephrine (NE) changes, in patients with sequelae of tuberculosis (TBsq). Cardiopulmonary exercise testings were performed in 49 TBsq patients and 9 controls. Each group had a break point in the dyspnea, plasma lactate, and plasma NE changes during exercise, all of which occurred at a similar exercise point. In TBsq patients in both exercise phases before and after the dyspnea break point, the dyspnea-slope (a dagger Borg scale/a dagger minute ventilation) correlated with the pH-slope (a dagger pH/a dagger oxygen uptake) (r = -0.616, p &lt; 0.0001; r = -0.629, p &lt; 0.0001, respectively, before and after the break point) and with the NE-slope (a dagger NE/a dagger oxygen uptake) (r = 0.443, p = 0.0012; r = 0.643, p &lt; 0.0001, respectively, before and after the break point). In TBsq patients during exercise, increases in circulating NE levels and exertional acidosis were correlated with exertional dyspnea.

DOI： 10.1007/s12576-009-0083-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

CD4(+)CD25(+) regulatory T (Treg) cells cause immune suppression by inhibiting T cell effector functions and play pivotal roles not only in self-tolerance but also in immune response to parasitic microbial pathogens. Mycobacteria are major parasitic bacterial pathogens, but the role of CD4(+)CD25(+) Treg cells in mycobacterial infection is not yet defined. In this study we found that, at the early stage of infection, depletion of CD25(+) cells reduced both bacterial load and granuloma formation in mice infected with Mycobacterium tuberculosis strains, such as M. tuberculosis Erdman or M. tuberculosis Kurono. However, at a later stage of infection, bacterial burden and histopathology were similar regardless of depletion of CD25(+) cells. Severe combined immunodeficient (SCID) mice reconstituted with CD4(+)CD25(-) T cells alone or a combination of CD4(+)CD25(+) and CD4(+)CD25(-) T cells showed similar bacterial loads and survival kinetics after infection with M. tuberculosis Erdman. Consistent with in vivo data, in vitro studies revealed that mycobacterial antigens, purified protein derivative of tuberculin (PPD), failed to induce the suppressive function of CD4(+)CD25(+) Treg cells to CD4(+)CD25(-) effector T cells, as demonstrated by the lack of response of CD4(+)CD25(+) T cells to PPD, in mice chronically infected with Mycobacterium bovis bacillus Calmette-Guerin and M. tuberculosis. Our data show that CD4(+)CD25(+) Treg cells have a transient effect at the early stage of mycobacterial infection but, contrary to the expectation, have little impact on the overall course of infection.

DOI： 10.1093/intimm/dxp126

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

CD4(+)CD25(+) regulatory T (Treg) cells cause immune suppression by inhibiting T cell effector functions and play pivotal roles not only in self-tolerance but also in immune response to parasitic microbial pathogens. Mycobacteria are major parasitic bacterial pathogens, but the role of CD4(+)CD25(+) Treg cells in mycobacterial infection is not yet defined. In this study we found that, at the early stage of infection, depletion of CD25(+) cells reduced both bacterial load and granuloma formation in mice infected with Mycobacterium tuberculosis strains, such as M. tuberculosis Erdman or M. tuberculosis Kurono. However, at a later stage of infection, bacterial burden and histopathology were similar regardless of depletion of CD25(+) cells. Severe combined immunodeficient (SCID) mice reconstituted with CD4(+)CD25(-) T cells alone or a combination of CD4(+)CD25(+) and CD4(+)CD25(-) T cells showed similar bacterial loads and survival kinetics after infection with M. tuberculosis Erdman. Consistent with in vivo data, in vitro studies revealed that mycobacterial antigens, purified protein derivative of tuberculin (PPD), failed to induce the suppressive function of CD4(+)CD25(+) Treg ce

DOI： 10.1093/intimm/dxp126

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL PUBLISHING, INC  

Background and objective: Exertional dyspnoea limits patients with IPF in their activities of daily living. The mechanism, however, has not been elucidated. This study tested the hypothesis in IPF that exertional dyspnoea correlates with cardiopulmonary exercise responses, specifically changes in arterial blood pH and plasma norepinephrine (NE).
Methods: Cardiopulmonary exercise testing with measurements of dyspnoea (Borg scale), plasma NE, plasma lactate and arterial blood gases were performed in 29 patients with IPF and in nine controls.
Results: Both groups showed obvious break points in dyspnoea changes during exercise. In IPF, an abrupt change in the Borg scale, pH, PaCO(2) and plasma NE occurred in the late exercise phase after the &apos;break point&apos;. Compared with controls, patients with IPF had significantly higher HCO(3)(-) levels and physiologic dead space/tidal volume during exercise. In IPF, during both exercise phases, the dyspnoea slope (Delta Borg scale/Delta minute ventilation) correlated with the pH slope (Delta pH/Delta oxygen uptake) (before the break point: r = -0.537, P = 0.0022; r = -0.886, P &lt; 0.0001, after the break point) and the NE slope (Delta NE/Delta oxygen uptake) (before the break point: r = 0.481, P = 0.0075; R = 0.784, P &lt; 0.0001, after the break point).
Conclusions: In patients with IPF, exercise-induced acidosis and increases in circulating NE levels were associated with intensity of exertional dyspnoea.

DOI： 10.1111/j.1440-1843.2009.01607.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATL INST INFECTIOUS DISEASES  

Medical treatment of pulmonary Mycobacterium avium complex (MAC) disease does not always provide curative effects and is frequently hampered by recurrence. This suggests the presence of a reservoir for MAC in the environment surrounding patients. We previously reported the recovery of MAC isolates from the residential bathrooms of outpatients. In the present study, to ascertain the colonizing sites and the possibility of an MAC reservoir in the bathrooms of patients, we tested the recovery and the genetic diversity of MAC isolates from 6 sites of specimens, including 2 additional sampling sites, inside the showerhead and the bathtub inlet, in the residential bathrooms of patients with pulmonary MAC disease. MAC isolates were recovered from 15 out of the 29 bathrooms (52%), including specimens from 14 bathtub inlets and 3 showerheads. Nearly half of these bathrooms (7/15) contained MAC strains that were identical or similar to their respective clinical isolates. Additionally, in 5 out of 15 bathrooms, polyclonal colonization was revealed by pulsed-field gel electrophoresis. The results imply that colonization of MAC organisms in the bathrooms of MAC patients occurs predominantly in the bathtub inlets, and there is thus a risk of infection and/or reinfection for patients via use of the bathtub and other sites in the bathroom.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD  

Mycobacterium avium complex (MAC) disease has been increasing worldwide not only in immunocompromised but also in immunocompetent humans. However, the relationship between mycobacterial strain virulence and disease progression in immunocompetent humans is unclear. In this study, we isolated 6 strains from patients with pulmonary MAC disease. To explore the virulence, we examined the growth in human THP-1 macrophages and pathogenicity in C57BL/6 mice. We found that one strain, designated 198, which was isolated from a patient showing the most progressive disease, persisted in THP-1 cells. In addition, strain 198 grew to a high bacterial load with strong inflammation in mouse lungs and spleens 16 weeks after infection. To our knowledge, strain 198 is the first isolated MAC strain that exhibits hypervirulence consistently for the human patient, human macrophages in vitro, and even for immunocompetent mice. Other strains showed limited survival and weak virulence both in macrophages and in mice, uncorrelated to disease progression in human patients. We demonstrated that there is a hypervirulent clinical MAC strain whose experimental virulence corresponds to the serious disease progression in the patients. The existence of such strain suggests the involvement of bacterial virulence in the pathogenesis of pulmonary MAC disease in immunocompetent status. (c) 2008 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.micpath.2008.10.007

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：大阪市立大学  

CiNii Article

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

CiNii Article

CiNii Books

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Spatially resolved (SR) spectroscopy has enabled non-invasive and continuous measurement of muscle oxygen saturation during exercise. In patients with chronic obstructive pulmonary disease (COPD), skeletal muscle dysfunction has been widely studied histochemically and biochemically. However, impairment of muscle oxygenation during exercise has not been elucidated yet. Methods: We measured oxygen saturation in the vastus lateralis muscle (SmO 2) using SR spectrometry during incremental cycle exercise in 16 COPD patients and 10 age-matched healthy subjects. Results: Significant decrease in SmO2 was found at peak exercise compared with warm-up in both groups (56.9±6.0% to 47.3±6.8% in patients with COPD, p&lt
0.001
60.7±5.8% to 49.9±7.7% in healthy subjects, p&lt
0.01). The decrease in SmO2 was linear with respect to increase in work rate, and the slope of SmO2 was significantly steeper in COPD patients than in healthy subjects (-0.282±0.159 vs -0.107±0.057 %/Watt, p&lt
0.001). The slope of SmO2 in COPD patients significantly correlated with body mass index (BMI) (p&lt
0.01), peak percutaneous oxygen saturation (p&lt
0.05), and peak pulmonary oxygen consumption (p&lt
0.05). Stepwise regression analysis revealed that BMI was a significant determinant of the SmO2 slope (p=0.01). Conclusions: We conclude that oxygenation of peripheral muscle is impaired during exercise in COPD patients and that BMI contributes independently to the change of muscle oxygen saturation with exercise in COPD patients. SR spectroscopy will provide useful information for the study of the dynamics of muscle oxygenation in COPD patients.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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PubMed

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

CiNii Article

CiNii Books

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：英語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：英語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：(一社)日本結核病学会  

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：英語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

【目的】新潟県で開発・市販されているヤスダヨーグルト(以下YYG)は、メチシリン耐性黄色ブドウ球菌(methicillin-resistant Staphylococcus aureus;以下MRSA)に対して抗菌活性を示す。本研究の目的は、YYGのMRSAに対する抗菌活性成分を同定することである。【方法】1)抗菌活性の評価:ディスク拡散法により抗菌活性を検討した。2)YYGの遠心分離成分の抗菌活性の評価:YYGを4000rpm、15分の条件で遠心分離し、得られた上清および沈澱物成分について抗菌活性を評価した。3)抗菌活性を示す乳酸菌のYYGからの単離・同定:MRSA菌液を添加したMRS寒天培地にYYGを塗布し、37℃、24時間の好気培養を行った。阻止円を形成したコロニーを採取し、MRS液体培地を用いて24時間静置培養(37℃、好気条件)した。16S rRNA遺伝子解析を行い、抗菌活性を示す乳酸菌種を同定した。4)乳酸菌が産生する抗菌活性成分の同定:抗菌活性を示す乳酸菌培養液上清に対して加熱・限外濾過・アルカリ処理・消化酵素処理の各処理を行い、抗菌活性の変化を評価した。その結果から、抗菌活性成分の同定を試みた。5)培養条件が乳酸菌増殖に与える影響の検討:好気培養と嫌気培養、および静置培養と振盪培養による乳酸菌培養を行い、各培養条件と乳酸菌増殖、培養液上清pHおよび抗菌活性との関連をMann-WhitneyのU検定で解析した。また、培養液上清pHと抗菌活性の強さを検討した。【結果】1)抗菌活性の評価:ディスク拡散法により適切に抗菌活性を半定量的に評価することが可能であった。2)YYGの遠心分離成分の抗菌活性の評価:YYGの遠心分離成分のうち、沈澱物に強い抗菌活性を認めた。また、YYGをビーズ破砕した後に遠心分離すると、沈澱物の抗菌活性は消失した。よって、抗菌活性成分はYYGに含まれる乳酸菌が産生していると推測した。3)抗菌活性を示す乳酸菌のYYGからの分離・同定:16S rRNA遺伝子解析の結果、Lactobacillus delbrueckii subsp.bulgaricus(以下LDB)がMRSAに対する抗菌活性を示すことが判明した。4)乳酸菌が産生する抗菌活性成分の同定:LDB上清はアルカリ処理により抗菌活性が減弱または消失した。さらに、過酸化水素を分解するカタラーゼをLDB培養液に添加すると、抗菌活性が著明に減弱した。5)各培養条件における乳酸菌培養液の比較:静置培養は振盪培養に比べて菌の増殖がよく(P=0.002)、また上清のpHが有意に低下し(P=0.002)、抗菌活性は強かった(P=0.002)。一方、好気培養と嫌気培養の間では、菌の増殖、上清pH、抗菌活性のいずれも有意な差を認めなかった(P=0.310、P=0.589、P=1.000)。また、LDB培養液上清pHと阻止円径との間に強い負の相関関係を認めた(相関係数=-0.875、P&lt;0.001)。【結論】YYGのMRSAに対する抗菌活性は、YYGに含まれる乳酸菌LDBが産生する乳酸および過酸化水素によるものであることが示唆された。(著者抄録)

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記述言語：英語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：英語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語  

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記述言語：英語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本結核病学会  

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記述言語：英語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：英語   出版者・発行元：日本細菌学会  

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記述言語：日本語   掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）   出版者・発行元：科学評論社  

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その他リンク： http://search.jamas.or.jp/link/ui/2016139494

記述言語：日本語   出版者・発行元：新潟医学会  

【目的】消化管手術の周術期には、黄色ブドウ球菌などの皮膚常在菌による創部感染、絶食による腸内細菌叢の攪乱に伴うBacterial translocation、抗菌薬使用に伴うmethicillin-resistant Staphylococcus aureus(MRSA)などの薬剤耐性菌の出現が起こりうる。このような状況に対して応用的プロバイオティクスによる周術期感染制御を視野に、ヨーグルト製品のもつ抗菌効果の特性を微生物学的に解析した。【方法】新潟県で開発され市販されているヤスダヨーグルト(以下、YYG)に注目して、1)抗菌活性スペクトル(被験株:methicillin-sensitive Staphylococcus aureus(MSSA)ならびにMRSA臨床分離株、大腸菌株DH5α)、2)配合菌株の異なる他の5種の市販ヨーグルト製品との抗菌活性の相違、3)YYG各配合菌種(Yc-x11およびYc-180)の示す抗菌作用、および4)抗菌活性を示す分離画分について、ディスク法による阻止円形成により検討した。【結果】YYGは大腸菌に比してMSSAに優位な抗菌活性を示した。また、YYGはMRSA臨床分離株に対しても抗菌活性を示した。他製品との比較において、YYGは最も高い抗菌活性を示した。YYG配合菌種は、通常の低塩濃度培地上では抗菌活性を示したものの高塩濃度条件下では、その効果は減弱あるいは消失した。YYGの抗菌活性は、上清ではなく沈殿画分に認めた。【結論】YYGはMRSAを含む黄色ブドウ球菌に対する直接的な抗菌活性を示した。その抗菌効果は、特有の配合菌種に依拠する抗菌活性物質によることが示唆された。ヨーグルトの中でもYYGは極めて有望な抗菌性機能食品として、周術期感染制御に貢献できる可能性がある。(著者抄録)

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：日本バイオフィルム学会  

非結核性抗酸菌は世界中の土壌や水系の環境中にバイオフィルムを形成して広く分布しており、ヒトに日和見感染する。なかでもMycobacterium avium、Mycobacterium intracellulareによる肺感染症は近年世界中で増加している。不思議な事にヒト-ヒト感染の報告はないので環境から生成したエアロゾルを吸入して感染している。私たちはM.avium、M.intracellulareが家庭の浴室に生息しており浴室から感染する危険性を報告してきた。そこで環境中のM.aviumが形成するバイオフィルムの生態が感染性およびエアロゾル形成に関与していると考え、その生態を走査型電子顕微鏡で観察した。本研究では抗酸菌のバイオフィルムの細胞外マトリックスの構成成分として知られているglycopeptidolipidの欠損株を用いて生態を比較した。その結果、M.aviumは膜に覆われたバイオフィルムを構築した。その膜の下に小型の桿菌がぎっしり詰まっていた。その桿菌には細胞間マトリックスがほとんど認められなかった。glycopeptidolipid欠損株には、菌を覆う膜の形成は認められなかった。M.aviumが形成するバイオフィルムの生態学的特徴から、菌体は膜状バイオフィルムに守られて、膜の内側で増殖していることが示唆された。同時に細胞間マトリックスがないので膜の一部が破綻すると内側の菌が個々に飛び出しエアロゾル形成に寄与すると思われる。(著者抄録)

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：英語   出版者・発行元：日本細菌学会  

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記述言語：英語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸ケア・リハビリテーション学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸ケア・リハビリテーション学会  

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記述言語：日本語   出版者・発行元：日本バイオフィルム学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：英語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

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記述言語：日本語   出版者・発行元：(一社)日本結核病学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本結核病学会  

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記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本結核病学会  

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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