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Development of a novel antibacterial using bacteriophage and RNA targeting CRISPR system

Research Project

Project/Area Number 17K19570
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Pathology, Infection/Immunology, and related fields
Research InstitutionJichi Medical University

Principal Investigator

Cui Longzhu  自治医科大学, 医学部, 教授 (50306932)

Co-Investigator(Kenkyū-buntansha) 氣駕 恒太朗  自治医科大学, 医学部, 講師 (90738246)
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords薬剤耐性菌 / MRSA / mecA / CRISPR-Cas / バクテリオファージ / 耐性菌 / 耐性遺伝子 / キメラファージ / ファージ / 薬剤耐性遺伝子 / 新規抗菌治療法 / 抗菌ファージ / 選択的殺菌 / ファージセラピー / RNA 分解酵素 / 追尾ミサイル型抗菌治療法 / 細菌 / CRISPRシステム / 抗菌療法
Outline of Final Research Achievements

A CRISPR-Cas targeting the methicillin resistance gene mecA of MRSA was designed and loaded onto staphylococcal phage. It was tested by dropping it to MRSA and MSSA agar plates to confirm bactericidal plaques. Results showed that the generated chimericphage only killed MRSA strain, but not killed MSSA strain. Moreover, mecA deleted mutants of MRSA was not killed by this chimericphage, demonstrating its gene-specific killing activity. The above results indicate that the synthesis of a bactericidal chimericphage that specifically kills mecA-carrying bacteria has succeed.

Academic Significance and Societal Importance of the Research Achievements

本研究で、我々は薬剤耐性遺伝子を標的とするCRISPR-Cas13aをバクテリオファージに搭載させ、初めに狙った細菌を選択できに殺菌する新規殺菌技術を開発した。本技術は、薬剤耐性菌の蔓延が人類の健康を脅かす現代医療問題に対して、有効な解決策となりうる。

Report

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

    (26 results)

All 2019 2018 2017

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (18 results) (of which Invited: 1 results) Book (1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Complete Genome Sequence of the Methicillin-Resistant Staphylococcus aureus Strain JMUB3031, Isolated from a Patient with Fatal Community-Acquired Pneumonia2019

    • Author(s)
      Bintao Cui, Shinya Watanabe, Yusuke Sato’o, Fumiya Nihashi, Yoshifumi Aiba, Kotaro Kiga, Teppei Sasahara, Xin-Ee Tan, Moriyuki Kawauchi, Tanit Boonsiri, Kanate Thitiananpakorn, Yusuke Taki, Feng-Yu Li, Shiro Imokawa, Longzhu Cui
    • Journal Title

      Microbiology Resource Announcements

      Volume: 8 Issue: 4 Pages: 1-2

    • DOI

      10.1128/mra.01652-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of compensatory mutations associated with restoration of daptomycin-susceptibility in daptomycin non-susceptible methicillin-resistant Staphylococcus aureus2019

    • Author(s)
      Izumo Kanesaka, Shingo Fujisaki, Yoshifumi Aiba, Shinya Watanabe, Takashi Mikawa, Akiko Kanayama Katsuse, Hiroshi Takahashi, Longzhu Cui, Intetsu Kobayashi
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 25 Issue: 1 Pages: 1-5

    • DOI

      10.1016/j.jiac.2018.09.009

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Complete genome sequencing of three human clinical isolates of Staphylococcus caprae reveals virulence factors similar to those of S. epidermidis and S. capitis2018

    • Author(s)
      Watanabe Shinya、Aiba Yoshifumi、Tan Xin-Ee、Li Feng-Yu、Boonsiri Tanit、Thitiananpakorn Kanate、Cui Bintao、Sato’o Yusuke、Kiga Kotaro、Sasahara Teppei、Cui Longzhu
    • Journal Title

      BMC Genomics

      Volume: 19 Issue: 1 Pages: 810-810

    • DOI

      10.1186/s12864-018-5185-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induction of Mucosal Humoral Immunity by Subcutaneous Injection of an Oil-emulsion Vaccine against <i>Salmonella enterica</i> subsp. <i>enterica</i> serovar Enteritidis in Chickens2018

    • Author(s)
      Ishida Yuuichi、Sakai Eishi、Sato Katsuo、Sugiyama Einori、Mima Kazuyuki、Taneno Akira、Shimomura Hirofumi、Cui Longzhu、Hirai Yoshikazu
    • Journal Title

      Food Safety

      Volume: 6 Issue: 4 Pages: 151-155

    • DOI

      10.14252/foodsafetyfscj.2018003

    • NAID

      130007546578

    • ISSN
      2187-8404
    • Related Report
      2018 Annual Research Report
  • [Journal Article] Optimized universal protocol for electroporation of both coagulase-positive and -negative Staphylococci2018

    • Author(s)
      Sato'o Yusuke、Aiba Yoshifumi、Kiga Kotaro、Watanabe Shinya、Sasahara Teppei、Hayakawa Yasuhiko、Cui Longzhu
    • Journal Title

      Journal of Microbiological Methods

      Volume: 146 Pages: 25-32

    • DOI

      10.1016/j.mimet.2018.01.006

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 狙った細菌を選択的に殺菌する殺菌技術の開発2019

    • Author(s)
      氣駕 恒太朗、李 峰宇、XinEe Tan、佐藤 祐介、渡邊 真弥、相羽 由詞、 Rodrigo Ibarra 、Jos R Penad、鈴木 仁人、崔 龍洙
    • Organizer
      第92回 日本細菌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] レプトトリキア科細菌由来のCRISPR-Cas13システムの機能解析2019

    • Author(s)
      Bintao Cui、渡邊 真弥、氣駕 恒太朗、相羽 由詞、河内 護之、Tanit Boonsiri、Kanate Thitiananpakorn、佐藤 祐介、XinEe Tan、崔 龍洙
    • Organizer
      第92回 日本細菌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 3.黄色ブドウ球菌のSaPI-phageシステムを利用した殺菌キメラファージの合成 Generation of bactericidal chimeric phages using SaPI-phage system of Staphylococcus aureus2019

    • Author(s)
      XinEe Tan、氣駕 恒太朗、渡邊 真弥、佐藤 祐介、相羽 由詞、河内 護之、Kanate Thitiananpakorn、 Rodrigo Ibarra 、R Penad、崔 龍洙
    • Organizer
      第92回 日本細菌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 酵母を利用したキメラファージ合成技術の開発2019

    • Author(s)
      河内 護之、氣駕恒太朗、李峰宇、Boonsiri TanitTan XinEe、佐藤祐介、相羽由詞、Kanate Thitiananpakorn、渡邊真弥、崔龍洙
    • Organizer
      第92回 日本細菌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 渡邊真弥、李峰宇、氣駕恒太朗、相羽由詞、佐藤祐介、Xin-Ee Tan、河内護之、Tanit Boonsiri、Kanate Thitiananpakorn、崔龍洙2019

    • Author(s)
      緑膿菌に広く感染するファージの分離・同定
    • Organizer
      第92回 日本細菌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 大腸菌に広く感染するファージの分離・同定2019

    • Author(s)
      李 峰宇、氣駕 恒太朗、渡邊 真弥、佐藤 祐介、相羽 由詞、河内 護之、XinEe Tan、Tanit Boonsiri、Kanate Thitiananpakorn、崔 龍洙
    • Organizer
      第92回 日本細菌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ファージによる細菌感染症治療モデルの確立2019

    • Author(s)
      佐藤 祐介、李 峰宇、氣駕 恒太朗、渡邊 真弥、相羽 由詞、河内 護之、XinEe Tan、Tanit Boonsiri、Kanate Thitiananpakorn、崔 龍洙
    • Organizer
      第92回 日本細菌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 抗菌ファージの開発に資する耐性菌の収集とMRSAファージの分離および同定2019

    • Author(s)
      相羽由詞、Xin-Ee Tan、Kanate Thitiananpakorn、渡邊真弥、氣駕恒太朗、佐藤祐介、Tanit Boonsiri、河内護之、李峰宇、崔龍洙
    • Organizer
      第92回 日本細菌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Genetic mechanism of high susceptibility to beta-lactam in Oxacillin-susceptible Methicillin-resistant Staphylococcus aureus2018

    • Author(s)
      渡邊真弥, Tanit Boonsiri, Kanate Thitiananpakorn, 相羽由詞, 佐藤祐介, 氣駕恒太朗, 笹原鉄平, 崔龍洙
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Establishment of a highly efficient electroporation protocol for Staphylococci2018

    • Author(s)
      佐藤祐介, 相羽由詞, 氣駕恒太郎, 渡邊真弥, 笹原鉄平, 早川靖彦, 崔龍洙
    • Organizer
      第91回日本細菌学会総会.
    • Related Report
      2017 Research-status Report
  • [Presentation] Identification of gene mutations associated with cross-resistance to daptomycin and vancomycin in Staphylococcus aureus.2018

    • Author(s)
      Kanate Thitiananpakorn, Yoshifumi Aiba, Shinya Watanabe, Yusuke Sato’o, Kotaro Kiga, Teppei Sasahara, Tanit Boonsiri, Feng-Yu Li and Longzhu Cui
    • Organizer
      第91回日本細菌学会総会.
    • Related Report
      2017 Research-status Report
  • [Presentation] Genetic mechanisms of high beta-lactam resistance in Methicillin-resistant Staphylococcus aureus.2018

    • Author(s)
      . Boonsiri Tanit, Watanabe Shinya, Thitiananpakorn Kanate, Sato’o Yusuke, Aiba Yoshifumi, Kiga Kotaro, Sasahara Teppei, Feng-Yu Li and Cui Longzhu
    • Organizer
      第91回日本細菌学会総会.
    • Related Report
      2017 Research-status Report
  • [Presentation] MRSAのβラクタム系抗菌薬耐性における遺伝学的多様性の解明2018

    • Author(s)
      . 相羽由詞, 渡邊真弥, 佐藤祐介, 氣駕恒太朗, Kanate Thitiananpakorn, Tanit Boonsiri, 李峰宇, 笹原鉄平, 崔龍洙
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Oxacillin感性を示すmecA陽性黄色ブドウ球菌のin vitro耐性化株の変異解析2017

    • Author(s)
      渡邊真弥, Tanit Boonsiri, Kanate Thitiananpakorn, 相羽由詞, 佐藤祐介, 氣駕恒太朗, 李峰宇, 笹原鉄平, 崔龍洙.
    • Organizer
      第66回日本感染症学会東日本地方会学術集会・第64回日本化学療法学会東日本支部総会 合同学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 黄色ブドウ球菌におけるダプトマイシン非感性化機序の遺伝学的特徴2017

    • Author(s)
      Thithiananpakon kanete1、相羽由詞、渡邊真弥、氣駕、佐藤、Boon、崔龍洙.
    • Organizer
      第66回日本感染症学会東日本地方会学術集会・第64回日本化学療法学会東日本支部総会 合同学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 医療の産業革命と抗菌薬耐性菌の問題について2017

    • Author(s)
      崔龍洙
    • Organizer
      日本華人教授会第14回年会国際シンポジウム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Oxacillin感性を示すmecA陽性黄色ブドウ球菌のOxacillin感性化機構の解明2017

    • Author(s)
      渡邊真弥, Tanit Boonsiri, Kanate Thitiananpakorn, 相羽由詞, 佐藤祐介, 氣駕恒太朗, 李峰宇, 笹原鉄平, 崔龍洙
    • Organizer
      第62回日本ブドウ球菌研究会.
    • Related Report
      2017 Research-status Report
  • [Presentation] Identification of gene mutations associated with decreased susceptibility to daptomycin and vancomycin in Staphylococcus aureus.2017

    • Author(s)
      Kanate Thitiananpakorn, Yoshifumi Aiba, Shiya Watanabe, Yusuke Sato’o, Tanit Boonsiri, Feng-Yu Li, Kotaro Kiga and Longzhu Cui
    • Organizer
      第62回日本ブドウ球菌研究会.
    • Related Report
      2017 Research-status Report
  • [Book] Precision Medicine 2019. ファージと現代医学2019

    • Author(s)
      氣駕 恒太朗, 崔 龍洙
    • Total Pages
      160
    • Publisher
      北隆館
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] PCT/JP2019/168012019

    • Inventor(s)
      崔龍洙、氣駕恒太朗
    • Industrial Property Rights Holder
      崔龍洙、氣駕恒太朗
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2018 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 特願2018-0977512018

    • Inventor(s)
      崔龍洙、氣駕恒太朗
    • Industrial Property Rights Holder
      崔龍洙、氣駕恒太朗
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-097751
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report

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Published: 2017-07-21   Modified: 2020-03-30  

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