Molecular characterization of novel isoniazid resistance mechanism in Mycobacterium tuberculosis

• Project/Area Number: 22790423
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Bacteriology (including Mycology)
• Research Institution: Research Institute, International Medical Center of Japan
• Principal Investigator: ANDO Hiroki 独立行政法人国立国際医療研究センター, 感染症制御研究部, 上級研究員 (70462786)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 結核 / 薬剤耐性 / イソニアジド

Research Abstract

Novel isoniazid (INH) resistance mutations were identified and characterized in Mycobacterium tuberculosis (Mtb). I collected INH-resistant Mtb clinical isolates and found that many of them have no mutations in known INH resistance genes. I identified several novel mutations in these isolates, and analyzed their roles in INH resistance.

Research Products

• [Journal Article] Downregulation of katG expression is associated with isoniazid resistance in Mycobacterium tuberculosis. (2011)
  • Author(s): Ando H, Kitao T, Miyoshi-Akiyama T, Kato S, Mori T, Kirikae T.
  • Journal Title: Mol Microbiol Volume: 79(6) Issue: 6 Pages: 1615-28
  • DOI: 10.1111/j.1365-2958.2011.07547.x
  • Peer Reviewed
• [Journal Article] Evaluation of a line probe assay for the rapid detection of gyrA mutations associated with fluoroquinolone resistance in multidrug-resistant Mycobacterium tuberculosis. (2011)
  • Author(s): Ando H, Mitarai S, Kondo Y, Suetake T, Kato S, Mori T, Kirikae T
  • Journal Title: J Med Microbiol Volume: 60(Pt 2) Issue: 2 Pages: 184-8
  • DOI: 10.1099/jmm.0.024729-0
  • Peer Reviewed
• [Journal Article] Downregulation of katG expression is associated with isoniazid resistance in Mycobacterium tuberculosis (2011)
  • Author(s): Ando H, Kitao T, Miyoshi-Akiyama T, Kato S, Mori T, Kirikae T.
  • Journal Title: Molecular Microbiology Volume: 79(6) Pages: 1615-1628
  • Peer Reviewed
• [Journal Article] Evaluation of a line probe assay for rapid detection of gyrA mutations associated with fluoroquinolone resistance in multidrug-resistant Mycobacterium tuberculosis (2011)
  • Author(s): Ando H, Mitarai S, Kondo Y, Suetake T, Kato S, Mori T, Kirikae T.
  • Journal Title: Journal of Medical Microbiology Volume: 60(Pt2) Pages: 184-188
  • Peer Reviewed
• [Journal Article] Pyrazinamide resistance in multidrug-resistant Mycobacterium tuberculosis isolates in Japan. (2010)
  • Author(s): Ando H, Mitarai S, Kondo Y, Suetake T, Sekiguchi JI, Kato S, Mori T, Kirikae T
  • Journal Title: Clin Microbiol Infect Volume: 16(8) Issue: 8 Pages: 1164-8
  • DOI: 10.1111/j.1469-0691.2009.03078.x
  • Peer Reviewed
• [Journal Article] Identification of katG mutations associated with high-level isoniazid resistance in Mycobacterium tuberculosis. (2010)
  • Author(s): Ando H, Kondo Y, Suetake T, Toyota E, Kato S, Mori T, Kirikae T
  • Journal Title: Antimicrob Agents Chemother Volume: 54(5) Issue: 5 Pages: 1793-9
  • DOI: 10.1128/aac.01691-09
  • Peer Reviewed
• [Journal Article] Pyrazinamide resistance in multidrug-resistant Mycobacterium tuberculosis isolates in Japan (2010)
  • Author(s): Ando H, Mitarai S, Kondo Y, Suetake T, Sekiguchi JI, Kato S, Mori T, Kirikae T.
  • Journal Title: Clinical Microbiology and Infection Volume: 16(8) Pages: 1164-1168
  • Peer Reviewed
• [Journal Article] Identification of katG mutations associated with high-level isoniazid resistance in Mycobacterium tuberculosis (2010)
  • Author(s): Ando H, Kondo Y, Suetake T, Toyota E, Kato S, Mori T, Kirikae T.
  • Journal Title: Antimicrobial Agents and Chemotherapy Volume: 54(5) Pages: 1793-1799
  • Peer Reviewed
• [Presentation] Downregulation of katG expression is associated with isoniazid resistance in Aycobacterium tuberculosis (2011)
  • Author(s): Ando H, Kitao T, Miyoshi-Akiyama T, Kato S, Mori T, Kirikae T.
  • Organizer: IUMS 2011 Congress
  • Place of Presentation: 札幌市,北海道,日本
  • Year and Date: 2011-09-10
• [Presentation] Mutations in the furA-katG intergenic region decrease katG expression and confer isoniazid resistance in Mycobacterium tuberculosis (2011)
  • Author(s): Ando H, Kitao T, Miyoshi-Akiyama T, Kato S, Mori T Kirikae T.
  • Organizer: 4^<th> Congress of European Microbiologists : FEMS 2011
  • Place of Presentation: ジュネーブ,スイス
  • Year and Date: 2011-06-27
• [Presentation] Downregulation of katG expression is associated with isoniazid resistance in Mycobacterium tuberculosis. (2011)
  • Author(s): Ando H, Kitao T, Miyoshi-Akiyama T, Kato S, Mori T, Kirikae T
  • Organizer: IUMS 2011 Congress
  • Place of Presentation: Japan(Poster No. P-BA28-23)
• [Presentation] Mutations in the furA-katG intergenic region decrease katG expression and confer isoniazid resistance in Mycobacterium tuberculosis. (2011)
  • Author(s): Ando H, Kitao T, Miyoshi-Akiyama T, Kato S, Mori T, Kirikae T
  • Organizer: 4^<th> Congress of European Microbiologists : FEMS 2011
  • Place of Presentation: Switzerland(Poster No. 67)
• [Presentation] Down-regulation of katG expression is associated with isoniazid resistance in Mycobacterium tuberculosis (2010)
  • Author(s): Ando H, Kato S, Mori T, Kirikae T.
  • Organizer: 110^<th> General Meeting of the American Society for Microbiology
  • Place of Presentation: San Diego, California, USA
  • Year and Date: 2010-05-27
• [Presentation] 結核菌のfabG1 遺伝子内サイレント変異によるイソニアジド耐性機序の解明 (2010)
  • Author(s): 安藤弘樹, 加藤誠也, 森亨, 切替照雄
  • Organizer: 第33回日本分子生物学会年会・第83 回日本生化学会大会合同大会
  • Place of Presentation: 兵庫県神戸市(ポスター番号 1P-1072)
• [Presentation] Down-regulation of katG expression is associated with isoniazid resistance in Mycobacterium tuberculosis. (2010)
  • Author(s): Ando H, Kato S, Mori T, Kirikae T
  • Organizer: 110^<th> General Meeting of the American Society for Microbiology
  • Place of Presentation: USA(Poster No. U-3153)