The mechanism of high methicillin resistance in Staphylococcus aureus
| Project/Area Number |
18590438
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Juntendo University |
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Principal Investigator |
CUI Longzhu Juntendo University, Medicine, Associate Professor (50306932)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Staphylococcus aureus / Drug resistance / Genome / Chromosomal point mutation / beta-lactam / 高度耐性化 / メチシリン耐性 / MRSA / Microarray / vraSR / graSR |
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| Research Abstract |
Methicillin resistance in Staphylococcus aureus is due to the acquisition of the low-affinity penicillin binding protein, PBP2A, encoded by mecA. However, there is lack of correlation between resistance levels and amount of PBP2A production leading to the conclusion that resistance to high levels of methicillin depends, in addition to PBP2A, on chromosomally encoded factors that are responsible for the strain-specific differences in resistance. The present study aims to investigate the factors affecting high methicillin resistance in MRSA. The study was started with isolating a set of isogenic MRSA strains with different level of methicillin resistance, and their whole genome sequences were determined. By comparing the genome sequence among the set of strains, candidate genes involved in high methicillin-resistant phenotype were identified and evaluated. Secondly, the genes identified as high methicillin-resistance associated in both this and our previous study, such as hmrA, hmrB, mgrA, graF and msrA2, were overexpressed in S.aureus to rise the level of methicillin resistance, and their transcriptional profiles for whole genome scale were compared each other, then the commonly regulated genes were identified to clarify the regulatory network of high methicillin resistance (HMR). The study conclusions are : 1) Fully expression of two component regulator system vraSR is necessary for HMR ; 2) regulatory gene sarH1 is deeply involved in HMR phenotype and 3) a novel mechanism, regulatory flip-flop genome inversion for HMR, was identified whereby HMR can achieved without chromosome mutation, but the detail deeded to be investigated.
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Report
(3 results)
Research Products
(19 results)
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[Presentation] Linezolid versus Vancomycin for methicillin-resistant Staphylococcus aureus infections2007
Author(s)
Michihiro, Uchiyama., Kyoko, Kuwahara., Yuki, Katayama., Tadashi, Baba., Longzhu, Cui., Keiichi, Hiramatsu
Organizer
ISAAR
Place of Presentation
Singapore
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] MRSA感染症におけるLinezolidの位置づけ-基礎的検討からの提言
Author(s)
内山, 倫宏, 桑原, 京子, 片山, 由紀, 崔, 龍洙, 馬場, 理, 平松, 啓一
Organizer
第55回日本化学療法学会総会
Place of Presentation
仙台
Description
「研究成果報告書概要(欧文)」より
Related Report
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