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Development of a novel antimicrobial method targeting conjugation systems of drug-resistant plasmid

Research Project

Project/Area Number 18K08455
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 InstitutionChugoku Gakuen University (2019-2020)
Kawasaki Medical School (2018)

Principal Investigator

Kawano Mitsuoki  中国学園大学, 公私立大学の部局等, 准教授(移行) (00455338)

Co-Investigator(Kenkyū-buntansha) 小椋 義俊  久留米大学, 医学部, 教授 (40363585)
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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords薬剤耐性菌 / バクテリオファージ / ファージセラピー / アンチセンスRNA / 遺伝子発現制御法 / 抗菌法 / 感染制御法 / 性線毛 / 薬剤耐性遺伝子 / 殺菌法 / 必須遺伝子 / 多剤耐性菌 / ファージ療法 / 抗菌薬 / カルバペネム耐性腸内細菌科細菌 / 生育阻害法 / 薬剤耐性細菌 / カルバペネム腸内細菌科細菌 / 薬剤耐性プラスミド / 接合伝達
Outline of Final Research Achievements

In this study, I carried out basic technology development of a novel phage therapy using a M13 phage-based genetic engineered phagemid, which combines characteristics of both phage and plasmid, to specifically target F-pili producing bacteria. This approach suppresses expression of essential genes in bacteria by antisense RNAs transcribed from the phagemid. Growth inhibited phenotypes were facilitated in hfq- conditions. Phage lysates were prepared from cells harboring phagemids as a lethal-agent delivery tool. Targeting the rpsM ribosome protein coding gene by phagemid-derived M13 phage infection of E. coli containing a carbapenem-producing F-plasmid and multidrug-resistant Klebsiella pneumoniae containing an F plasmid resulted in the death of over 99.99% of infected bacteria. This study provides a possible strategy for treating bacterial infection and can be applied to any F-pilus producing bacterial species.

Academic Significance and Societal Importance of the Research Achievements

畜産現場における抗菌薬の乱用が薬剤耐性菌を産生する主要な原因になっているが、ファージを用いた新規抗菌法は、代替法として畜産分野での実用化が期待できる。また、性線毛を産生するサルモネラ属菌や腸管出血性大腸菌O157などの食中毒菌を人に感染する前に食品や環境中から除菌する方法の開発につながる。さらに、水平伝播による薬剤耐性遺伝子の拡散防止や、新規薬剤耐性遺伝子による薬剤耐性菌の出現を遅らせることができ公衆衛生的な問題に貢献できる。これらは、医療費を含む社会的・経済的負担の大幅な軽減にもつながると考えられる。

Report

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

    (8 results)

All 2021 2020 2019

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

  • [Journal Article] Development of multiplexing gene silencing system using conditionally induced polycistronic synthetic antisense RNAs in Escherichia coli2021

    • Author(s)
      Fujita Shouta、Tsumori Yutaka、Makino Yuko、Saito Mineki、Kawano Mitsuoki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 556 Pages: 163-170

    • DOI

      10.1016/j.bbrc.2021.03.152

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antimicrobial antisense RNA delivery to F-pili producing multidrug-resistant bacteria via a genetically engineered bacteriophage2020

    • Author(s)
      Suzuki Yuya、Ishimoto Takumi、Fujita Shouta、Kiryu Sachie、Wada Mamoru、Akatsuka Takahiro、Saito Mineki、Kawano Mitsuoki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 530 Issue: 3 Pages: 533-540

    • DOI

      10.1016/j.bbrc.2020.06.088

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Artificial small RNA-mediated growth inhibition in Escherichia coli and Salmonella enterica serovar Typhimurium2020

    • Author(s)
      Kawano M, Morohashi S, Oda K, Ishikawa M, Fujita S, Saito M
    • Journal Title

      Biochemical Biophysical Research Communications

      Volume: 521(3) Issue: 3 Pages: 577-583

    • DOI

      10.1016/j.bbrc.2019.10.060

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Functional characterization of the type I toxin Lpt from Lactobacillus rhamnosus by fluorescence and atomic force microscopy2019

    • Author(s)
      Maggi S, Yabre K, Ferrari A, Lazzi C, Kawano M, Rivetti C, Folli C
    • Journal Title

      Scientific Reports

      Volume: 9(1) Issue: 1 Pages: 15208-15208

    • DOI

      10.1038/s41598-019-51523-z

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 抗菌アンチセンスRNA発現ファージを用いた薬剤耐性菌の殺菌法2021

    • Author(s)
      川野光興
    • Organizer
      第15回日本ゲノム微生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Phage-delivered antimicrobial antisense RNAs kill multidrug-resistant bacteria2020

    • Author(s)
      Mitsuoki Kawano
    • Organizer
      The 17th Young Scientist Seminar “Establishment of International Research Network for Bioresources and Their Utilization”
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] カルバペネム耐性腸内細菌に感染するファージの探索とファージバンクの設立に向けて2020

    • Author(s)
      川野光興
    • Organizer
      第93回日本細菌学会総会シンポジウム(ウインクあいち)2020年2月21日、シンポジウムコンビーナ・座長・口頭発表
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 連続グアニンRNA配列による大腸菌の生育阻害効果2019

    • Author(s)
      川野光興、諸橋祥太、石川雅峻、小田幸平、藤田翔太、齊藤峰輝
    • Organizer
      第42回日本分子生物学会年会(福岡国際会議場)2019年12月3日、ポスター発表
    • Related Report
      2019 Research-status Report

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

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