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Functional analysis and characterization of KatG mutations associated with isoniazid-resistant Mycobacterium tuberculosis and their crystal structures

Research Project

Project/Area Number 17K15695
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Bacteriology (including mycology)
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

KIM HYUN  国立感染症研究所, 細菌第二部, 主任研究官 (90648817)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsM.tuberculosis KatG / Isoniazid-resistance / 結晶構造解析 / 結核菌由来katG / イソニアジド耐性 / 結核菌 / KatG / 立体構造解析 / KatG変異 / Catalase-peroxidase 活性 / X線結晶構造解析 / 薬剤耐性
Outline of Final Research Achievements

As isoniazid (INH) is an integral first-line anti-tuberculosis drug, INH-resistant Mycobacterium tuberculosis has become an urgent global health problem. Mutations of several genes, such as katG, inhA, and ahpC in M. tuberculosis have been reported to be associated with INH-resistance. However, all specific mutation points involved in the resistance have not yet been determined.
In this study, we sequenced the whole genomes of 11 INH-resistant M. tuberculosis clinical isolates collected from Taiwan and found five novel mutants in the katG. KatG exhibits catalase and peroxidase activities and also activates INH. Therefore, it seems that these novel mutations in the katG are involved in INH-resistance. This study aimed to elucidate the interaction between novel mutants in the katG and INH-resistance.

Academic Significance and Societal Importance of the Research Achievements

本研究課題は積極的に国内外の学術研究会において発表するとともに、論文著書として広く公開する。ホームページや報道機関の発表、市民公開講座等を通じて、研究成果を一般国民に向けて分かりやすく発信することも予定している。また、研究成果のうち必要なものについては特許の申請を行い、他の研究者や研究機関において利用可能な状態にする。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (11 results)

All 2020 2019 2018

All Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (7 results)

  • [Journal Article] WQ-3810 inhibits DNA gyrase activity in ofloxacin-resistant Mycobacterium leprae2020

    • Author(s)
      Park Jong-Hoon、Yamaguchi Tomoyuki、Ouchi Yuki、Koide Kentaro、Mori Shigetarou、Kim Hyun、Mukai Tetsu、Nakajima Chie、Suzuki Yasuhiko
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 26 Issue: 4 Pages: 335-342

    • DOI

      10.1016/j.jiac.2019.10.013

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] WQ-3810: A new fluoroquinolone with a high potential against fluoroquinolone-resistant Mycobacterium tuberculosis2020

    • Author(s)
      Ouchi Yuki、Mukai Tetsu、Koide Kentaro、Yamaguchi Tomoyuki、Park Jong-Hoon、Kim Hyun、Yokoyama Kazumasa、Tamaru Aki、Gordon Stephen V.、Nakajima Chie、Suzuki Yasuhiko
    • Journal Title

      Tuberculosis

      Volume: 120 Pages: 101891-101891

    • DOI

      10.1016/j.tube.2019.101891

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] DNA gyrase could be a crucial regulatory factor for growth and survival of Mycobacterium leprae2019

    • Author(s)
      Kim Hyun、Fukutomi Yasuo、Nakajima Chie、Kim Youn Uck、Mori Shigetarou、Shibayama Keigo、Nakata Noboru、Suzuki Yasuhiko
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 10815-10815

    • DOI

      10.1038/s41598-019-47364-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mutations in Genes Encoding Penicillin-Binding Proteins and Efflux Pumps Play a Role in β-Lactam Resistance in Helicobacter cinaedi2018

    • Author(s)
      Emiko Rimbara, Shigetarou Mori, Hyun Kim, Masato Suzuki, Keigo Shibayama
    • Journal Title

      ANTIMICROBIAL AGENS AND CHEMOTHERAPHY

      Volume: 62(2)

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] BFF122 shows inhibitory activities against Mycobacterium tuberculosis and M. leprae DNA gyrases2020

    • Author(s)
      Hyun Kim, Yumi Maeda, Emiko Rimbara, Keigo Shibayama, Toshiki Tamura, Shigetarou Mori
    • Organizer
      第93回日本細菌学会・総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Antimicrobial resistance in Helicobacter cinaedi2020

    • Author(s)
      Emiko Rimbara, Shigetarou Mori, Hyun Kim, Masato Suzuki, Keigo Shibayama
    • Organizer
      第93回日本細菌学会・総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Crystal structure of a diadenosine tetraphosphate phosphorylase from Mycobacterium avium2020

    • Author(s)
      森茂太郎,本田尚子,金玄,林原絵美子,柴山恵吾
    • Organizer
      第93回日本細菌学会・総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Functional analysis of M. leprae DNA gyrase and its role in bacterial growth and survival2019

    • Author(s)
      Hyun Kim, Yasuo Fukutomi, Chie Nakajima, Youn Uck Kim, Shigetarou Mori, Keigo Shibayama, Naboru Nakata, Yasuhiko Suzuki
    • Organizer
      第92回日本細菌学会・総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Transcriptomic change by knockout of genes involving DNA modifications in Helicobacter cineadi2019

    • Author(s)
      Emiko Rimbara, Atsushi Toyoda, Shigetarou Mori, Hyun Kim, Keigo Shibayama
    • Organizer
      第92回日本細菌学会・総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Functional analysis of KatG mutations associated with isoniazid-resistance in M. tuberculosis2018

    • Author(s)
      Hyun Kim, Ruwen Jou, Shigetarou Mori, Emiko Rimbara, Keigo Shibayama
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Whole-genome phylogenetic analysis of Helicobacter cinaedi including isolates from nosocomial infection2018

    • Author(s)
      Emiko Rimbara, Masato Suzuki, Koji Yahara, Shigetarou Mori, Hyun Kim, Keigo Shibayama
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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