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Molecular characterization of antibiotic resistance mechanism in nontuberculous mycobacteria.

Research Project

Project/Area Number 21890309
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Bacteriology (including Mycology)
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

WACHINO Jun-Ichi  National Institute of Infectious Diseases, 細菌第二部, 主任研究官 (00535651)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥2,652,000 (Direct Cost: ¥2,040,000、Indirect Cost: ¥612,000)
Fiscal Year 2010: ¥1,261,000 (Direct Cost: ¥970,000、Indirect Cost: ¥291,000)
Fiscal Year 2009: ¥1,391,000 (Direct Cost: ¥1,070,000、Indirect Cost: ¥321,000)
Keywords非結核性抗酸菌 / 薬剤耐性 / ミコール酸 / クラリスロマイシン
Research Abstract

We generated a random transposon gene-knockout library of Mycobacterium avium to identify the genes responsible for antibiotic resistance. As a result, a variety of genes for efflux system, cell metabolism, and cell wall synthesis were identified as factors involved in antibiotic resistance. Among them, we focused on a kasB-knockout mutant (ΔkasB) strain and an MAV_2241-knockout mutant (ΔMAV_2241) strain, and characterized them in detail. The ΔkasB and ΔMAV_2241 strains showed the reduction in MICs (minimal inhibitory concentration) of various antibiotics including clarithromycin compared to that of wild-type strain. In addition, the ΔkasB strain increased susceptibility to the detergent such as SDS. Proteins involved in cell wall synthesis in Mycobacteria seem to be attractive target for antibiotic development.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (5 results)

All 2011 2010

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (2 results)

  • [Journal Article] Structural Insights into the Novel Diadenosine 5',5'''-P(1),P(4)-Tetraphosphate Phosphorylase from Mycobacterium tuberculosis H37Rv.2011

    • Author(s)
      Mori Shigetarou, Shibayama Keigo, Wachino Jun-ichi, Arakawa Yoshichika
    • Journal Title

      J Mol Biol. 410(1)

      Pages: 93-104

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Crystallization and preliminary X-ray analysis of the diadenosine 5',5'''-P1,P4-tetraphosphate phosphorylase from Mycobacterium tuberculosis H37Rv.2010

    • Author(s)
      Mori Shigetarou, Shibayama Keigo, Wachino Jun-ichi, Arakawa Yoshichika
    • Journal Title

      Acta Crystallogr Sect F Struct Biol Cryst Commun 66(Pt3)

      Pages: 279-81

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Purification and molecular characterization of a novel diadenosine 5',5'''-P(1),P(4)-tetraphosphate phosphorylase from Mycobacterium tuberculosis H37Rv.2010

    • Author(s)
      Mori Shigetarou, Shibayama Keigo, Wachino Jun-ichi, Arakawa Yoshichika
    • Journal Title

      Protein Expr Purif. 9(1)

      Pages: 99-105

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] 結核菌由来新規diadenosine 5',5'''-P1,P4-tetraphosphate加リン酸分解酵素の機能構造解析2010

    • Author(s)
      森茂太郎、柴山恵吾、和知野純一、荒川宜親
    • Organizer
      日本生物工学会2010年度大会
    • Place of Presentation
      福岡
    • Related Report
      2010 Final Research Report
  • [Presentation] 結核菌由来新規diadenosine 5',5'''-P1,P4-tetraphosphate加リン酸分解酵素の結晶構造解析2010

    • Author(s)
      森茂太郎、柴山恵吾、和知野純一、荒川宜親
    • Organizer
      日本農芸化学会2010年度大会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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