• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Alterations in the DNA topoisomerase IV responsible for quinolone resistance in MRSA and MRSE

Research Project

Project/Area Number 08670325
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionKyoto Pharmaceutical University

Principal Investigator

NISHINO Takeshi  Kyoto Pharmaceutical University, Department of Microbiology, Professor, 薬学部, 教授 (50097838)

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)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
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)
KeywordsDNA gyrase / Topoisomerase IV / Quinolone / MRSA / MRSE / Resistance / Topo IV
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.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Masatoshi Tanaka: "Mutation in DNA gyrase of norfloxacin-resistant clinical isolates of Neisseria gonorrhoese." Genitourin.Med.72. 295-297 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nobuhisa Masuda: "In vitro and vivo antibacterial of CS-940,a new 6-fluoro-8-difluoromethoxy quinolone." Antimicrob.Agents.Chemother.40. 1201-1207 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masakuni Ozaki: "Structure-antibacterial activities of thiazolo and thiazetoquinolone derivatives." Biol.Pharm.Chemother.19. 1457-1462 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 西野 武志: "細菌学への招待6抗菌薬における耐性メカニズム." Guardian Angel. 2. 2-5 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshie Takahashi: "In vitro activity of HRS-903,a new quinolone." Antimicrob.Agents Chemother.41. 1326-1330 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masatoshi Tanaka, Masako Otsuki, Takeshi Nishino, Intetsu Kobayashi, Tetsuro Matsumoto, Joichi Kumazawa: "Mutation in DNA gyrase of norfloxacin-resistant clinical isolates of Neisseria gonorrhoeae." Genitourin.Med. Vol.72. 295-297 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nobuhisa Masuda, Yoshie Takahashi, Masako Otsuki, Etsuyo Ibuki, Hidenobu Miyoshi, Takeshi Nishino: "In vitro and in vivo antibacterial activities of CS-940, a new 6-fluoro-8-difluoromethoxy quinolone." Antimicrob.Agents Chemother. Vol.40. 1201-1207 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masakuni Ozaki, Jun Segawa, Masahiko Kitano, Yoshifumi Tomii, Takuya Honmura, Masato Matsuda, Masahiro Kise, Takeshi Nishino: "Structure-antibacterial activity and cytotoxicity relationships of thiazolo and thiazetoquinolone derivatives." Biol.Pharm.Bull. Vol.19. 1457-1462 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takeshi Nishino: "Mechanism of resistance in microorganisms." Gurdian Angel. Vol.2. 2-5 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshie Takahashi, Nobuhisa Masuda, Masako Otsuki, Takeshi Nishino: "In vitro activity of HSR-903, a new quinolone." Antimicrob.Agents Chemother. Vol.41. 1326-1330 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Jun Igari, Matsuhisa Inoue, Takeshi Nishino et al.: "Survey of sensitivities of clinical isolates to antibacterial agents (Annual report)." Jpn.J.Antibiotics. Vol.50. 683-703 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshie Takahashi: "In vitro activity of HSR-903,a new quinolone." Antimicrob.Agents Chemother.41. 1326-1330 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 猪狩淳: "臨床材料分離菌の各種抗菌薬に対する感受性サーベイランス(1年次報告)" JPN.J.Antibiotics. 50. 683-703 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Masakuni Ozaki: "Structure-antibacterial activity and cytotoxicity relationships of thiazolo and thiazetoquinolone derivatives" Biol.Pharm.Bull.19. 1457-1462 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nobuhisa Masuda: "In vitro and in vivo antibacterial activities of CS-940,a new 6-fluoro-8-difluoromethoxy quinolone" Antimicrob.Agents Chemother.40. 1201-1207 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Masatoshi Tanaka: "Mutation in DNA gyrase of norfloxacin-resistant clinical isolates of Neisseria gonorrhoeae" Genitourin.Med.72. 295-297 (1996)

    • Related Report
      1996 Annual Research Report

URL: 

Published: 1996-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi