| Project/Area Number |
09470078
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
HIRAMATSU Keiichi Juntendo university the medical department Professor, 医学部, 教授 (10173262)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Kazumi Juntendo university the medical department Assistant, 医学部, 助手 (90276478)
堀 典子 順天堂大学, 医学部, 助手 (50245700)
KUWAHARA Kyoko Juntendo university the medical department Assistant, 医学部, 助手 (10167976)
HANAKI Hideaki Juntendo university the medical department Lecture, 医学部, 講師 (60286747)
ITO Teruyo Juntendo university the medical department Lecture, 医学部, 講師 (10095763)
KONDO Noriko Juntendo university the medical department Assistant
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥10,600,000 (Direct Cost: ¥10,600,000)
Fiscal Year 1998: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1997: ¥7,100,000 (Direct Cost: ¥7,100,000)
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| Keywords | VRSA / hetero-VRSA / vancomycin / Staphylococcus aureus / peptidoglycan / cell wall / teicoplanin / glycopeptide / ムレインモノアー / 疫学 / PBP / genotyping / 細胞壁合成 |
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| Research Abstract |
The mechanism of vancomycin resistance was looked for with the vancomycin-resistant Staphylococcus aureus strain Mu5O and the heterogeneously vancomycin-resistant Staphylococcus aureus strain Mu3. The cell wall synthesis of these strains were activated as demonstrated with accelerated incorporation of N-acetylglucosamine into the cell wall, increased intracellular murein monomer precursor pooi, and increased cell wall thickness. Biochemical analysis of cell wall peptidoglycan showed decreased cross-linking, which correlated with 2.4 times increased vancomycin binding to the purified peptidoglycan of Mu5O as compared with that of vancomycin-susceptible strains of MRSA as well as MSSA.Incidence of hetero-VRSA was 9.3% of all MRSA isolates in university hospitals in Japan and 1.3% in non-uuniversity hospitals and clinics. Since we have shown that hetero-VRSA spontaneously generates VRSA at a high frequency of 1 in 1,000,000 on vancomycin selection, and hetero-VRSA itself causes vancomyicn therapeutic failure, the situation was interpreted as a greatly alarming one. A combination therapy against MRSA strains (sulbactam/ampicillin plus arbekacin) was developed to counter failure of vancomycin therapy. Several cases were experienced with this treatment regimen with success. Teicoplanin, a newly introduced glycopeptide, was found out to have less antimicrobial acitivity against hetero-VRSA and VRSA than vancomycin. Thus, development of novel therapeutic agents against VRSA is an urgent task.
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