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2007 Fiscal Year Final Research Report Summary

The mechanism of high methicillin resistance in Staphylococcus aureus

Research Project

Project/Area Number 18590438
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

CUI Longzhu  Juntendo University, Medicine, Associate Professor (50306932)

Project Period (FY) 2006 – 2007
KeywordsStaphylococcus aureus / Drug resistance / Genome / Chromosomal point mutation / beta-lactam
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.

  • Research Products

    (13 results)

All 2008 2007 2006 Other

All Journal Article (6 results) (of which Peer Reviewed: 3 results) Presentation (7 results)

  • [Journal Article] A Mutated Response-Regulator graR is Responsible for Hetero-VISA to VISA Phenotypic Conversion of Vancomycin Resistance2008

    • Author(s)
      H.Neoh, L.Cui and K.Hiramatsu
    • Journal Title

      Antimicorb.Agents Chemother 52

      Pages: 45-53

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] A Mutated Response-Regulator graR is Responsible for Hetero-VISA to VISA Phenotypic Conversion of Vancomycin Resistance. Antimicorb2008

    • Author(s)
      Hui-min, Neoh, Longzhu, Cuil, Fumihiko, Takeuchi, Miki, Matsuo and Keiichi, Hiramatsu
    • Journal Title

      Antimicorb. Agents Chemother Vol. 52(1)

      Pages: 45-53

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Subinhibitory concentrations of β-lactam induce haemolytic activity in Staphylococcus aureus through the SaeRS two-component system2007

    • Author(s)
      H.Kuroda, M.Kuroda, L.Cui and K.Hiramatsu
    • Journal Title

      FEMS Microbiology letters 268

      Pages: 98-105

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Subinhibitory concentrations of β -lactam induce haemolytic activity in Staphylococcus aureus through the SaeRS two-component system2007

    • Author(s)
      Hiroko, Kuroda, Makoto, Kuroda, Longzhu, Cui and Keiichi, Hiramatsu
    • Journal Title

      FEMS Microbiology letters Vol. 268

      Pages: 98-105

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cross-resistance of Vancomycin-intermediate Staphylococcus aureus to Daptomycin and Vancomycin2006

    • Author(s)
      L.Cui, E., Tominaga, H.Neoh and K.Hiramatsu
    • Journal Title

      Antimicorb.Agents Chemother 50

      Pages: 1079-1082

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Correlation between Reduced Daptomycin Susceptibility and Vancomycin resistance in Vancomycin-intermediate Staphylococcus aureus. 5tv2006

    • Author(s)
      Longzhu, Cui, . Eiji, Tominaga, . Hui-min, Neoh., Keiichi, Hiramatsu
    • Journal Title

      Antimicorb. Agents Chemother Vol. 50(3)

      Pages: 1079-1082

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 黄色ブドウ球菌のゲノムFlip-Flop逆位2007

    • Author(s)
      崔 龍洙
    • Organizer
      第80回日本細菌学会総会
    • Place of Presentation
      大阪
    • Year and Date
      20070400
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] On graSR system. GRC on Staphylococcal diseases2007

    • Author(s)
      Longzhu, Cui., Hui-min, Neoh., Keiichi, Hiramatsu
    • Organizer
      Les Diablerets
    • Place of Presentation
      Switzerland
    • Year and Date
      20070000
    • Description
      「研究成果報告書概要(欧文)」より
  • [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
    • Year and Date
      20070000
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] A Mutated Response-Regulator graR is Responsible for Hetero-VISA to VISA Phenotypic Conversion of Vancomycin Resistance in Staphylococcus aureus2007

    • Author(s)
      Longzhu, Cui., Hui-min, Neoh., Keiichi, Hiramatsu
    • Organizer
      ISAAR
    • Place of Presentation
      Singapore
    • Year and Date
      20070000
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Two-component regulatory system GraSR isinvolved in converting Mu3 from hetero-VISA into VISA phenotype2007

    • Author(s)
      Hui-min, Neoh., 崔, 龍洙., 平松, 啓一
    • Place of Presentation
      第80回日本細菌学会総会(大阪)
    • Year and Date
      20070000
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 黄色ブドウ球菌のゲノムFlip-Flop逆位2007

    • Author(s)
      崔龍洙., Hui-min, Neoh., 平松, 啓一
    • Place of Presentation
      第80回日本細菌学会総会(大阪).(Workshop presentation)
    • Year and Date
      20070000
    • Description
      「研究成果報告書概要(欧文)」より
  • [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

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Published: 2010-02-04  

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