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Analysis of mycobacterial non-coding RNA promotes the fundamental understanding for newly developing antimycobacterial therapies and strategies.

Research Project

Project/Area Number 19K08938
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54030:Infectious disease medicine-related
Research InstitutionTokyo Metropolitan Geriatric Hospital and Institute of Gerontology (2020-2021)
Tokyo Women's Medical University (2019)

Principal Investigator

Yoshida Atsushi  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (40364541)

Co-Investigator(Kenkyū-buntansha) 菊池 賢  東京女子医科大学, 医学部, 教授 (60214748)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords迅速発育抗酸菌 / 同定 / 薬剤感受性 / 誘導耐性 / ゲノム解析 / non-coding RNA / 抗酸菌 / ゲノム / 治療 / 感染症
Outline of Research at the Start

1.迅速発育抗酸菌(RGM)のnon-coding RNAに関する基礎的検討
我々は既に全国から収集した臨床分離RGM(400株以上)について同定・薬剤耐性のデータを得ている。これまでの全ゲノムデータから、RGMの病原性や薬剤耐性に関わりうるnon-coding RNA領域の候補を探し、それらが臨床分離株でどのように保有されているのか、変異は何か、解析する。
2.non coding RNAと薬剤感受性との相関および新規抑制物質の探索
1.の研究から新たな候補物質探索の可能性の見通しを明らかにする。一方でnon-coding RNA領域を修飾し、菌の増殖抑制を来しうる候補物質/方法を探索する。

Outline of Final Research Achievements

More than 500 strains of rapidly growing mycobacteria (RGM) were collected from all over Japan, and the results of gene identification, drug susceptibility, and macrolide resistance mechanism were obtained. We were able to report the differences in bacterial species between specimens and isolated areas, and proposed new treatment options for M. abscessus infection.
Whole-genome analysis of isolates revealed genetic features of RGM including mobile elements, and accumulation of SNP mutations over time in 5 strains of M. abscessus subsp. abscessus, which were derived from the same patient and acquired inducible resistance to multiple drugs. By comparing these five strains, we have found RNA whose expression is increased under the administration of clarithromycin, and we are conducting a detailed analysis.

Academic Significance and Societal Importance of the Research Achievements

多数の迅速発育抗酸菌の臨床分離株を用いた解析により、アルベカシン、シタフロキサシン、リファブチンが治療選択のオプションとなりうることを示した。さらに下気道検体では有意にM. abscessusの割合が高いこと、北日本では有意にM. abscessusの分離割合が高いことを見出した。一方ゲノム解析では、臨床分離株はしばしば外来性の因子を有すること、さらに複数の薬剤に誘導耐性を有しても、SNPの変異数はそれほど多くは増加しないことが明らかになった。転写レベルでの変化が主体であると推測されたが、関与するRNA、non-coding RNAの同定には、条件検討を含む詳細な解析が必要であった。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (11 results)

All 2022 2021 2020 2019

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (6 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] Nationwide surveillance of antimicrobial susceptibility of 509 rapidly growing mycobacteria strains isolated from clinical specimens in Japan.2021

    • Author(s)
      Kamada K, Yoshida A, Iguchi S, Arai Y, Uzawa Y, Konno S, Shimojima M, Kikuchi K.
    • Journal Title

      Sci Rep

      Volume: 11 Issue: 1 Pages: 12208-12208

    • DOI

      10.1038/s41598-021-91757-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Geographical distribution and regional differences in 532 clinical isolates of rapidly growing mycobacterial species in Japan.2021

    • Author(s)
      Kamada K,Yoshida A, Iguchi S, Arai Y, Uzawa Y, Konno S, Shimojima M, Kikuchi K.
    • Journal Title

      Sci Rep

      Volume: 11 Issue: 1 Pages: 4960-4960

    • DOI

      10.1038/s41598-021-84537-7

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pulmonary infection due to fluoroquinolone-resistant Mycolicibacterium fortuitum: a case report.2020

    • Author(s)
      Kurokawa K, Harada N, Sasano H, Takagi H, Takei S, Nakamura A, Kamada K, Yoshida A, Kikuchi K, Takahashi K.
    • Journal Title

      BMC Infect Dis

      Volume: 20 Issue: 1 Pages: 866-866

    • DOI

      10.1186/s12879-020-05596-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mycolicibacterium wolinskyiによる人工膝関節置換術後膝関節炎の1例.2020

    • Author(s)
      15.德田美香,曽木広信,吉田 敦,阿保一茂,松谷 暁,水島 遼,鎌田啓佑,板倉泰朋,井口成一,鵜澤 豊,荒井裕子,菊池 賢.
    • Journal Title

      日本臨床微生物学雑誌

      Volume: 30 Pages: 80-83

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 迅速発育抗酸菌感染症の治療選択2022

    • Author(s)
      吉田 敦,鎌田啓佑,菊池 賢
    • Organizer
      日本臨床微生物学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Key note lecture 9 比較的まれな非結核性抗酸菌症の臨床と検査2021

    • Author(s)
      吉田 敦,鎌田啓佑,菊池 賢
    • Organizer
      日本臨床微生物学会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 肺外の迅速発育抗酸菌感染症の治療選択 従来の薬剤の限界と新規薬剤の応 用2020

    • Author(s)
      吉田 敦、鎌田啓佑、板倉泰朋、井口成一、鵜澤 豊、菊池 賢
    • Organizer
      第95回日本結核・非結核性抗酸菌症学会総会・学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] 日本におけるM. fortuitumのニューキノロン系抗菌薬に対する感受性とQRDR領域の遺伝子変異の関係2019

    • Author(s)
      鎌田啓佑、吉田 敦、板倉泰朋、井口成一、鵜澤 豊、菊池 賢
    • Organizer
      日本感染症学会東日本地方会
    • Related Report
      2019 Research-status Report
  • [Presentation] Geographical Distribution and Regional Difference among Clinical Isolates of Rapidly Growing Mycobacterial Species in Japan2019

    • Author(s)
      Kamada K, Yoshida A, Mizushima R, Itakura Y, Iguchi S, Arai Y, Uzawa Y, Shimojima M, Kikuchi K.
    • Organizer
      European Congress of Clinical Microbiology and Infectious Diseases
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Antimicrobial Susceptibilities to 24 drugs of 491 Rapidly Growing Mycobacteria from Clinical Isolates in Japan2019

    • Author(s)
      Kamada K. Yoshida A, Mizushima R, Itakura Y, Iguchi S, Arai Y, Uzawa Y, Shimojima M, Kikuchi K.
    • Organizer
      European Congress of Clinical Microbiology and Infectious Diseases
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Book] 今日の疾患辞典2019

    • Author(s)
      吉田 敦
    • Publisher
      株式会社プレシジョン
    • Related Report
      2019 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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