Alterations in the DNA topoisomerase IV responsible for quinolone resistance in MRSA and MRSE
| Project/Area Number |
08670325
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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 | Kyoto Pharmaceutical University |
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Principal Investigator |
NISHINO Takeshi Kyoto Pharmaceutical University, Department of Microbiology, Professor, 薬学部, 教授 (50097838)
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| Co-Investigator(Kenkyū-buntansha) |
MASAKO Otsuki Kyoto Pharmaceutical University, Department of Microbiology, Assistant, 薬学部, 助手 (30121552)
GOTOH Naomasa Kyoto Pharmaceutical University, Department of Microbiology, Associate Professor, 薬学部, 助教授 (30121156)
後藤 直正 京都薬科大学, 薬学部, 講師 (30121560)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | DNA gyrase / Topoisomerase IV / Quinolone / MRSA / MRSE / Resistance / Topo IV |
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| Research Abstract |
We tried to determine partial sequences of the gyrA and parC genes of clinical isolates of Staphylococcus epidermidis and Staphylococcus aureus and attempted to assess the association of mutations in the gyrA and parC genes with fluoroquinolone resistance in MRSA and MRSE Sequence analysis of PCR products from 65 fluoroquinolone-resistant clinical isolates of MRSA was used to examine the quinolone resistance-determining regions of the gyrA gene and the analogous regions of the parC gene. The changes of the serine at position 80 (Ser 80) in parC of 65 strains ested were associated with resistance to quinolone antibacterials. Moreover, sequential acquisition of mutations in parC and gyrA led to higher levels of resistance. These data strongly suggest that ParC mutations as well as GyrA mutations are also important factor for fluoroquinolone resistance in MRSA.
Seven fluoroquinolone-resistant mutants of MRSE were examined for mutations in the gyrA and parC genes. While five mutants had a single amino acid changes in ParC,two higher level fluoroquinolone-resistant isolates had a double amino acid change in GyrA (Ser84-Try & Asp94-Gly) and a single amino acid change in ParC.The most important factor for quinolone resistance in S.epidermidis including MRSE seems to be the mutations of target enzymes such as DNA gyrase and DNA topoisomerase IV,and mutations causing decreased drug accumulation due to decreased drug penetration and/or increased drug efflux.
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Report
(3 results)
Research Products
(16 results)
