Identification of genetic factors responsible for multidrug resistance of methicillin-resistant Staphylococcus aureus (MRSA)
Project/Area Number |
24590093
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Biological pharmacy
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Research Institution | Juntendo University |
Principal Investigator |
MATSUO Miki 順天堂大学, 医学部, 助教 (70320322)
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | 薬剤耐性機構 / 黄色ブドウ球菌 / 耐性変異 / VISA / MRSA / バンコマイシン / slow-VISA / hVISA / sVISA / rpoC mutation / relQ mutation / 細胞壁肥厚化 / cmk / ゲノム解析 / ゲノムシークエンス / バンコマイシン耐性 |
Outline of Final Research Achievements |
Vancomycin-intermediate Staphylococcus aureus (VISA) affects the sensitivity of not only glycopeptides (vancomycin and teicoplanin) but also daptomycin. To understand the overall vancomycin resistance mechanism of VISA, we performed whole genome sequencing of 45 VISA strains isolated by vancomycin selection, and identified mutations using a comparative genome analysis. The results indicated that mutations in rpoB and rpoC genes, in addition of two-component regulatory systems, led to changes in the flow of metabolites, and caused increased peptidoglycan production and reduced autolytic activity. We also found that the functional alteration of the genes in multiple metabolic pathways in addition to those with regulatory functions can achieve hVISA-to-VISA phenotypic conversion. This explains the high frequencies of hVISA-to-VISA conversion and the characteristic shape of the population curves of hetero-VISA strains.
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] "Slow VISA," a novel phenotype of vancomycin resistance, found in vitro in heterogeneous vancomycin-intermediate Staphylococcus aureus strain Mu3.2014
Author(s)
Saito M, Katayama Y, Hishinuma T, Iwamoto A, Aiba Y, Kuwahara-Arai K, Cui L, Matsuo M, Aritaka N, Hiramatsu K
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Journal Title
Antimicrob Agents Chemother
Volume: 58
Issue: 9
Pages: 5024-5035
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Genomic Basis for Methicillin Resistance in Staphylococcus aureus.2013
Author(s)
Hiramatsu K, Ito T, Tsubakishita S, Sasaki T, Takeuchi F, Morimoto Y, Katayama Y, Matsuo M, Kuwahara-Arai K, Hishinuma T, Baba T.
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Journal Title
Infect Chemother
Volume: 45(2)
Issue: 2
Pages: 117-136
DOI
Related Report
Peer Reviewed
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