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Molecular analysis of isoniazid-resistant Mycobacterium tuberculosis

Research Project

Project/Area Number 18K07121
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49050:Bacteriology-related
Research InstitutionJuntendo University

Principal Investigator

Kirikae Teruo  順天堂大学, 医学部, 教授 (50192563)

Co-Investigator(Kenkyū-buntansha) 竹本 訓彦  国立研究開発法人国立国際医療研究センター, その他部局等, 上級研究員 (40546793)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords結核 / 薬剤耐性 / イソニアジド耐性 / 薬剤耐性遺伝子 / イソニアジド耐性遺伝子 / 中等度耐性 / 全ゲノム解析 / 系統樹解析 / 結核菌 / InhA / katG / 薬剤耐性結核菌 / イソニアジド / カタラーゼ・ペルオキシダーゼ / KatG
Outline of Final Research Achievements

Drug-resistant Mycobacterium tuberculosis isolates were obtained from 254 patients (202 Japan-born and 52 foreign-born) in Japan. The whole genome sequences and lineages of these isolates were determined and phylogenetic trees were constructed. Of the 254 isolates, 54 were multidrug-resistant. The percentages of multidrug-resistant isolates were significantly higher in foreign-born than Japan-born patients. Nine multidrug-resistant isolates were extensively drug-resistant and obtained from Japan-born patients. A significant number of multidrug-resistant M. tuberculosis strains were isolated from foreign-born patients. Foreign-derived isolates affect the nationwide genetic diversity of drug-resistant M. tuberculosis in Japan. Extensively drug-resistant M. tuberculosis isolates were transmitted among the Japanese population. This study was summarized in the following paper;
Mizukoshi F et al: Molecular Epidemiology of Drug-Resistant Mycobacterium Tuberculosis in Japan, mSphere, in press.

Academic Significance and Societal Importance of the Research Achievements

全国で分離された薬剤耐性結核菌の全ゲノム情報を解析し、その性状や分布、遺伝子系統、薬剤耐性に関与する遺伝子について解析した。これらの結果、日本人と外国人の患者由来薬剤耐性結核はそれぞれ異なる系統の分類を示した。外国人由来の多剤耐性結核菌の割合は日本人由来結核菌の割合より優位に大きかった。外国人由来薬剤耐性結核菌は日本全国の薬剤耐性結核の多様性に優位に影響していた。超多剤耐性結核は日本人の間で伝播していることが分かった。これらの基礎データは、日本における薬剤耐性結核対策の基礎資料を提供する。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report

Research Products

(3 results)

All 2019 2018

All Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Presentation] 薬剤耐性結核菌の全ゲノムを用いた分子疫学解析2019

    • Author(s)
      水越文徳、小林信之、切替富美子、切替照雄、舩渡川圭次、桐谷礼子
    • Organizer
      第57回栃木県公衆衛生学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 次世代シークエンサーによる結核菌の全ゲノム解析を用いた薬剤耐性結核の診断および治療法の開発に関する研究2019

    • Author(s)
      小林信之
    • Organizer
      第2回NHOネットワーク会議
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Whole genome sequencing analysis of Mycobacterium tuberculosis isolates from patients with drug-resistant tuberculosis in Japan2018

    • Author(s)
      Nobuyuki Kobayashi, Akiko Ichinose, Tohru Miyoshi-Akiyama, Teruo Kirikae, Fuminori Mizukoshi, Jin Takasaki, Ken Ohta
    • Organizer
      49th Union World Conference on Lung Health
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-01-27  

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