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Using zebrafish to understand the ribosomal modification in pathogenic bacteria

Research Project

Project/Area Number 26670210
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Bacteriology (including mycology)
Research InstitutionChiba University

Principal Investigator

Takaya Akiko  千葉大学, 薬学研究科(研究院), 准教授 (80334217)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords23S rRNAメチル化酵素 / 薬剤感受性 / グラム陽性菌 / ゼブラフィッシュ / 23SrRNA / 内因性メチル化酵素 / 病原性 / 抗菌薬耐性 / 肺炎球菌 / 23SrRNAメチル化酵素 / TEL感受性 / 修飾制御
Outline of Final Research Achievements

Some ribosome-targeting antibiotics can inhibit bacterial growth by binding to 23SrRNA and interfering with protein synthesis. i) We have found that RlmCD-mediated U747 methylation promotes efficient G748 methylation by RlmAII, facilitating the binding of telithyromycin, a 23SrRNA-targeting antibiotic, to the ribosome in Streptococcus pneumoniae. ii) Linezolid (LZD) is an antibiotic used for the treatment of serious infections caused by multidrug-resistant Gram-positive bacteria including MRSA. We analyzed LZD-resistant CoNS isolated in Japan. Resistance to LZD has been associated with a G2576U mutation in 23SrRNA, which is close to the binding region of LZD. Furthermore, all LZD-resistant isolates had mutations in the gene encoding RlmN methyltransferase. iii) The infection model using zebrafish was difficult to examine the role of the intrinsic methylation of nucleotides in 23S rRNA for the bacterial pathogenesis.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (8 results)

All 2015 2014 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (3 results) Remarks (2 results)

  • [Journal Article] RlmCD-mediated U747 methylation promotes efficient G748 methylation by methyltransferase RlmAⅡ in 23S rRNA in Streptococcus pneumoniae; interplay between two rRNA methylations responsible for telithromycin susceptibility.2015

    • Author(s)
      Shoji T, Takaya A, Sato Y, Kimura S, Suzuki T, Yamamoto T
    • Journal Title

      Nucleic Acids Research

      Volume: 43 Issue: 18 Pages: 8964-72

    • DOI

      10.1093/nar/gkv609

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular characterization of linezolid-resistant CoNS isolates in Japan.2015

    • Author(s)
      Takaya A, Kimura A, Sato Y, Ishiwada N, Watanabe M, Matsui M, Shibayama K, Yamamoto T.
    • Journal Title

      J. Atimicrob. Chemother.

      Volume: 70 Issue: 3 Pages: 658-663

    • DOI

      10.1093/jac/dku443

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Linezolid-resistant Staphylococcus epidermidis associated with long-term, repeated linezolid use in a pediatric patient.2015

    • Author(s)
      Ishiwada N, Takaya A, Kimura A, Watanabe M, Hino M, Ochiai H, Matsui M, Shibayama K, Yamamoto T.
    • Journal Title

      J Infect Chemother.

      Volume: 22 Issue: 3 Pages: 187-190

    • DOI

      10.1016/j.jiac.2015.10.004

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 臨床分離メチシリン耐性Coagulase-negative Staphylococcus におけるリネゾリド耐性化機構2015

    • Author(s)
      木村旭、高屋明子、石和田稔彦、山本友子
    • Organizer
      第98回日本細菌学会関東支部総会
    • Place of Presentation
      東京歯科大学
    • Year and Date
      2015-10-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] 肺炎球菌23SrRNAのメチル化とテリスロマイシン感受性2015

    • Author(s)
      高屋明子、庄司竜麻、山本 友子
    • Organizer
      第17回日本RNA学会年会
    • Place of Presentation
      ホテルライフォート札幌
    • Year and Date
      2015-07-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] 肺炎球菌のテリスロマイシン感受性に寄与するrRNA内因性修飾2014

    • Author(s)
      庄司竜麻,高屋明子,木村聡,鈴木勉,佐藤慶治,山本友子
    • Organizer
      第97 回日本細菌学会関東支部総会
    • Place of Presentation
      東京ドームホテル
    • Year and Date
      2014-10-30
    • Related Report
      2014 Research-status Report
  • [Remarks] 千葉大学大学院薬学研究院微生物薬品化学研究室ホームページ

    • URL

      http://www.p.chiba-u.jp/lab/bisei/index.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 千葉大学大学院薬学研究院ホームページ

    • URL

      http://www.p.chiba-u.jp/lab/bisei/index.html

    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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