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Development of new therapeutic agents for clarithromycin-resistant pulmonary MAC disease

Research Project

Project/Area Number 17K10041
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Infectious disease medicine
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

Nakata Noboru  国立感染症研究所, ハンセン病研究センター 感染制御部, 室長 (70237296)

Co-Investigator(Kenkyū-buntansha) 星野 仁彦  国立感染症研究所, ハンセン病研究センター 感染制御部, 室長 (20569694)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords肺MAC症 / クラリスロマイシン / 薬剤耐性 / MAC症 / マクロライド / Mycobacterium avium
Outline of Final Research Achievements

In order to develop an effective therapeutic agent against clarithromycin-resistant pulmonary MAC disease, we measured the effects of 37 avermectin derivatives using highly clarithromycin-resistant MAC strains derived from patients with pulmonary MAC disease. We found 5 derivatives that show antibacterial activity against the MAC strains. It was suggested that these five species target an unknown molecule, not the Domein V 2057-2059 site of the 50S ribosome, which is the known target site of macrolides. It was clarified that these five derivatives also exerted antibacterial effect against intracellular MAC, and the antibacterial activity was higher than that of ivermectin.

Academic Significance and Societal Importance of the Research Achievements

肺MAC 症を含む肺NTM 症治療においてもっとも重要な治療薬がクラリスロマイシンであるが、クラリスロマイシンの長期投与により耐性菌が出現することが知られており、クラリスロマイシン耐性肺NTM 症に対しては有効な経口投与抗菌薬は存在しないのが現状である。in vitro、及び培養細胞レベルではあるが、アベルメクチン誘導体がクラリスロマイシン耐性MACに有効であることが示され、クラリスロマイシンとは異なる機序で作用していることが示唆されたことは、新たな治療薬開発にとっての前進である。

Report

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

    (2 results)

All 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (1 results)

  • [Journal Article] A rapid and non-pathogenic assay for association of Mycobacterium tuberculosis gyrBA mutations and fluoroquinolone resistance using recombinant Mycobacterium smegmatis2018

    • Author(s)
      Yoshida Mitsunori、Nakata Noboru、Miyamoto Yuji、Fukano Hanako、Ato Manabu、Hoshino Yoshihiko
    • Journal Title

      FEMS Microbiology Letters

      Volume: 365 Issue: 23 Pages: 1-8

    • DOI

      10.1093/femsle/fny266

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] CAM耐性MACに対する新規合成マクロライドの効果2018

    • Author(s)
      星野仁彦、深野華子、野口吉彦、吉田光範、朝倉崇徳、森野英里子、中川拓、長谷衣佐乃、高崎仁、小川賢二、長谷川直樹、阿戸学、中田登、砂塚敏明
    • Organizer
      第49回結核・非定形抗酸菌症治療研究会
    • Related Report
      2018 Research-status Report

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

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