2000 Fiscal Year Final Research Report Summary
Epidemiology of MRSA in the world and mechanism of vancomycin resistance
| Project/Area Number |
11800006
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| Research Category |
Grant-in-Aid for Special Purpose.
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| Allocation Type | Single-year Grants |
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| Research Institution | JUNTENDO UNIVERSITY |
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Principal Investigator |
HIRAMATSU Keiichi Juntendo University School of Mdeicine, Department of Bacteriology Professor, 医学部, 教授 (10173262)
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| Co-Investigator(Kenkyū-buntansha) |
CUI Longzhu Juntendo Unversity School of Medicine, Department of Bacteriology Assistant, 医学部, 助手 (50306932)
HANAKI Hideaki Juntendo Unversity School of Medicine, Department of Bacteriology Lecturer, 医学部, 講師 (60286747)
ITO Teruyo Juntendo University School of Medicine, Department of Bacteriology Lecturer, 医学部, 講師 (10095763)
KURODA Makoto Juntendo Unversity School of Medicine, Department of Bacteriology Assistant, 医学部, 助手 (80317411)
BABA Tadashi Juntendo Unversity School of Medicine, Department of Bacteriology Assistant, 医学部, 助手 (30317458)
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| Project Period (FY) |
1999 – 2000
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| Keywords | MRSA / SCCmec / ccrA / ccrB / VRSA / hetero-VRSA / cell wall / vancomycin |
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| Research Abstract |
We showed that the methicillin-resistance-specific DNA found in Japanese type of MRSA is a novel mobile genetic element whose movement is driven by two novel recombinase genes. We designated the element Staphylococcus cassette chromosome mec (SCCmec) and its recombinase cassette chromosome recombinase A and B (ccrA and ccrB). Subsequently, we tested MRSA strains from the world and found that there are three alleles in SCCmec : type-I, -II, and -III.Geographical distribution of the SCCmec was performed, and found out that most of the Asian countries possessed type-I or type-III SCCmec whereas, Japan and Korea had type-II SCCmec carrying MRSA strains. We proceeded to show that type-II SCCmec carrying strains are more prone to generate vancomycin-resistant S.aureus (VRSA) which was in agreement with the dissemination of many hetero-VRSA and VRSA strains in Korea and Japan. A novel type of hetero-VRSA was found in Thailand for the first time in South Eastern Asian countries, having type-III SCCmec. As expected, the strain showed quite different susceptibility pattern to glycopeptide antibiotics than those found in type-II SCCmec. The former was less resistant and was more unstable in its phenotypic expression. Mechanism of glycopeptide resistance was investigated in Mu5O, the first VRSA strain isolated in Japan in 1997. The strain had increased production of murein monomer precursor, the constituent of cell-wall peptidoglycan. Increased activities of the enzymes involved in cell-wall synthesis pathway were demonstrated and there was a striking thickening of cell wall by observation with transmission electronscopy. By developing a new detection system for a slight difference in the level of glycopeptide resistance, we succeeded in demonstrating close correlation between cell-wall thickeness and the level of vancomycin resistance.
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