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Analysis of bioactive compounds released by bacteria for early detection

Research Project

Project/Area Number 21K16318
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54030:Infectious disease medicine-related
Research InstitutionOsaka University

Principal Investigator

Yamasaki Seiji  大阪大学, 高等共創研究院, 准教授 (70757301)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords耐性菌 / 感染症 / 排出ポンプ / 細菌 / 抗生物質 / 抗菌薬 / 薬剤耐性 / 多剤耐性
Outline of Research at the Start

治療困難な耐性菌への対応は、国を挙げて取り組まなければならない大きな問題となっている。耐性菌を出現させないためには、抗菌薬の適正使用が最も重要であり、速やかに原因菌とその薬剤耐性能に適した薬を用いた治療を行うことが求められている。

よって本研究では、即日での菌種同定と耐性菌検出を可能にする、細菌の迅速分析技術の基盤を構築する。具体的には、多数の遺伝子組み換え菌株を用いて解析技術の開発・条件の最適化を行うことで、臨床で必要とされている迅速な菌種同定・耐性菌検出に向けた、細菌由来放出化合物測定法を構築する。

Outline of Final Research Achievements

This research found that current signals with specific shapes reflecting cell size and ion leakage were generated by potential differences in a micropore-based bridge circuit and identified three bacterial species by classifying signal shapes using machine learning.
In addition, we discovered several common mutations in the bacterial drug efflux pump, which is responsible for the efflux of antibiotics and bioactive compounds from bacteria, present in drug-resistant Pseudomonas aeruginosa. We were able to submit the paper as an achievement that will lead to the development of a rapid method for determining bacterial resistance.
Furthermore, by analyzing and classifying the gases generated from the culture medium using machine learning, we succeeded in identifying bacterial species. The number of bacterial species is currently increasing and further analysis is underway for practical use.

Academic Significance and Societal Importance of the Research Achievements

早期に菌種の同定および耐性菌の検出ができれば、不要な抗菌薬投与を減らすことができ、細菌感染症による死亡者数を減らせるだけでなく、新たな耐性菌出現の抑制、医療費の削減にも大きく貢献することができる。研究期間全体を通じて、当目的の達成に寄与する新デバイスの開発に向けた技術基盤を構築することができた。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (46 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (2 results) Journal Article (14 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 13 results,  Open Access: 11 results) Presentation (29 results) (of which Int'l Joint Research: 6 results,  Invited: 13 results) Remarks (1 results)

  • [Int'l Joint Research] 国立農学研究所(フランス)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] 香港大学(中国)

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Changes in the expression of <i>mexB</i>, <i>mexY</i>, and <i>oprD</i> in clinical <i>Pseudomonas aeruginosa</i> isolates2024

    • Author(s)
      Y. Matsumoto, S. Yamasaki, K. Hayama, R. Iino, H. Noji, A. Yamaguchi, and K. Nishino
    • Journal Title

      Proceedings of the Japan Academy, Series B

      Volume: 100 Issue: 1 Pages: 57-67

    • DOI

      10.2183/pjab.100.006

    • ISSN
      0386-2208, 1349-2896
    • Year and Date
      2024-01-11
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a bacterial release compound assay for prevention and early detection of bacteria-derived diseases2024

    • Author(s)
      S. Yamasaki, N. Koga, T. Hosomi, M. Zwama, C. Jirayupat, T. Yanagida, and K. Nishino
    • Journal Title

      Medical Science Digest

      Volume: 50 Pages: 41-43

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intestinal and fecal pH in human health2023

    • Author(s)
      R. Yamamura, KY. Inoue, K. Nishino, and S. Yamasaki
    • Journal Title

      Frontiers in Microbiomes

      Volume: 2 Pages: 1192316-1192316

    • DOI

      10.3389/frmbi.2023.1192316

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Drug resistance and physiological roles of RND multidrug efflux pumps in Salmonella enterica, Escherichia coli and Pseudomonas aeruginosa2023

    • Author(s)
      Yamasaki Seiji、Zwama Martijn、Yoneda Tomohiro、Hayashi-Nishino Mitsuko、Nishino Kunihiko
    • Journal Title

      Microbiology

      Volume: 169 Issue: 6 Pages: 001322-001322

    • DOI

      10.1099/mic.0.001322

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comprehensive analysis of the binding site for efflux transporter inhibitors in Pseudomonas aeruginosa2023

    • Author(s)
      S. Yamasaki, M. Zwama, N. Koga, K. Sakurai, R. Nakashima, A. Yamaguchi, and K. Nishino
    • Journal Title

      BIO Clinica

      Volume: 38 Pages: 74-78

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Investigating multidrug efflux pumps associated with fatty acid salt resistance in Escherichia coli2023

    • Author(s)
      Yamasaki Seiji、Yoneda Tomohiro、Ikawa Sota、Hayashi-Nishino Mitsuko、Nishino Kunihiko
    • Journal Title

      Frontiers in Microbiology

      Volume: 14 Pages: 954304-954304

    • DOI

      10.3389/fmicb.2023.954304

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vanadyl Naphthalocyanine-Doped Polymer Dots for Near-Infrared Light-Induced Nitric Oxide Release and Bactericidal Effects2023

    • Author(s)
      Liu Zuoyue、Okada Yuta、Ichinose Yuma、Saitoh Daisuke、Ieda Naoya、Yamasaki Seiji、Nishino Kunihiko、Nakagawa Hidehiko、Fujitsuka Mamoru、Osakada Yasuko
    • Journal Title

      ACS Applied Nano Materials

      Volume: 6 Issue: 2 Pages: 1487-1495

    • DOI

      10.1021/acsanm.2c05566

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Drug resistance and physiological roles of RND multidrug efflux pumps in Salmonella enterica, Escherichia coli, and Pseudomonas aeruginosa2023

    • Author(s)
      Seiji Yamasaki, Martijn Zwama, Tomohiro Yoneda, Mitsuko Hayashi-Nishino, Kunihiko Nishino
    • Journal Title

      Microbiology

      Volume: -

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibitor binding pits analysis of bacterial multidrug efflux transporters for new drug development2022

    • Author(s)
      Seiji Yamasaki、Martijn Zwama、Naoki Koga、Keisuke Sakurai、Ryosuke Nakashima、Akihito Yamaguchi、Kunihiko Nishino
    • Journal Title

      Precision Medicine

      Volume: 5 Pages: 56-60

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Spatial Characteristics of the Efflux Pump MexB Determine Inhibitor Binding2022

    • Author(s)
      Yamasaki Seiji、Koga Naoki、Zwama Martijn、Sakurai Keisuke、Nakashima Ryosuke、Yamaguchi Akihito、Nishino Kunihiko
    • Journal Title

      Antimicrobial Agents and Chemotherapy

      Volume: 66 Issue: 11

    • DOI

      10.1128/aac.00672-22

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of the drug efflux pump in the intrinsic cefiderocol resistance of <i>Pseudomonas aeruginosa</i>2022

    • Author(s)
      Ikawa Sota、Yamasaki Seiji、Morita Yuji、Nishino Kunihiko
    • Journal Title

      bioRxiv

      Volume: -

    • DOI

      10.1101/2022.05.31.494263

    • Related Report
      2022 Research-status Report
    • Open Access
  • [Journal Article] Evaluation of efflux pump inhibitors of MexAB- or MexXY-OprM in Pseudomonas aeruginosa using nucleic acid dyes2022

    • Author(s)
      Masasuke Fujiwara, Seiji Yamasaki, Yuji Morita, Kunihiko Nishino
    • Journal Title

      Journal of infection and chemotherapy

      Volume: 28 Issue: 5 Pages: 595-601

    • DOI

      10.1016/j.jiac.2022.01.003

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of multidrug efflux transporters in resistance to fatty acid salts reveals a TolC-independent function of EmrAB in Salmonella enterica2022

    • Author(s)
      Yoneda Tomohiro、Sakata Hiroki、Yamasaki Seiji、Hayashi-Nishino Mitsuko、Nishino Kunihiko
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 4 Pages: e0266806-e0266806

    • DOI

      10.1371/journal.pone.0266806

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Function and Inhibitory Mechanisms of Multidrug Efflux Pumps2021

    • Author(s)
      Nishino Kunihiko、Yamasaki Seiji、Nakashima Ryosuke、Zwama Martijn、Hayashi-Nishino Mitsuko
    • Journal Title

      Frontiers in Microbiology

      Volume: 12 Pages: 737288-737288

    • DOI

      10.3389/fmicb.2021.737288

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 健康な愛玩動物由来ステノトロフォモナスマルトフィリアのキノロン耐性機構2024

    • Author(s)
      齋藤博 、山崎聖司 、西野邦彦 、山岸純一
    • Organizer
      日本薬学会第144年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 細菌共存学の開拓と発展-ヒトと病原細菌・腸内細菌との新たな関係の構築-2024

    • Author(s)
      山崎聖司
    • Organizer
      ラボバタカイギin SeekSxpot
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] ポリマードットを活用した新規抗菌剤の開発2024

    • Author(s)
      山崎聖司、小阪田泰子
    • Organizer
      SAKIGAKEクラブメンバー交流会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Development of Universal Inhibitors of Drug Efflux Pumps to Overcome Multidrug-Resistant Bacteria2024

    • Author(s)
      K. Nishino, M. Zwama, S. Yamasaki, M. Fujiwara, M. Shoji
    • Organizer
      Meeting with CARB-X and Japanese researchers
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of Universal Inhibitors of Drug Efflux Pumps to Overcome Multidrug-Resistant Bacterial Infections2024

    • Author(s)
      S. Yamasaki, K. Nishino
    • Organizer
      National Centre for Global Health and Medicine (NCGM) and Sir Howard Dalton Centre (HDC), the University of Warwick Joint Japan/ UK Science and Policy workshop
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 薬剤耐性菌によるパンデミックの阻止に向けた細菌薬剤排出ポンプの構造解析と阻害剤探索2023

    • Author(s)
      山崎聖司
    • Organizer
      日本感染症医薬品協会メディカル・サイエンス セミナー
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 消毒薬クロルヘキシジンに曝露したアシネトバクター属の多剤交差耐性機序―排出ポンプおよびポーリンの発現解析を中心としてー2023

    • Author(s)
      川井眞好、山崎聖司、西野邦彦、山岸純一
    • Organizer
      日本化学療法学会西日本支部総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] パンデミック回避に向けた薬剤耐性菌性状解析ナノデバイスの開発2023

    • Author(s)
      山崎聖司、柳田剛
    • Organizer
      JASIS
    • Related Report
      2023 Annual Research Report
  • [Presentation] 細菌共存学の開拓と発展-ヒトと病原細菌・腸内細菌との新たな関係の構築-2023

    • Author(s)
      山崎聖司
    • Organizer
      ナノ薬剤研究会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 細菌共存学の開拓と発展-ヒトと病原細菌・腸内細菌との新たな関係の構築-2023

    • Author(s)
      山崎聖司
    • Organizer
      チーム阪大project Meeting
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] パンデミック回避に向けた薬剤耐性菌性状解析ナノデバイスの開発2023

    • Author(s)
      山崎聖司
    • Organizer
      人と知と物質で未来を創るクロスオーバーアライアンス活動報告会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 耐性菌感染症の治療薬開発に向けた細菌薬剤排出ポンプの阻害剤結合ピットの解析2023

    • Author(s)
      山崎聖司、古閑修輝、Martijn Zwama、櫻井啓介、中島良介、山口明人、西野邦彦
    • Organizer
      チーム阪大Project Meetingリトリート
    • Related Report
      2023 Annual Research Report
  • [Presentation] 耐性菌感染症の克服に向けた薬剤排出ポンプ阻害剤の結合部位解析2023

    • Author(s)
      山崎聖司、古閑修輝、Martijn Zwama、櫻井啓介、中島良介、山口明人、西野邦彦
    • Organizer
      日本生化学会近畿支部例会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Efflux pump's spatial properties control inhibitor binding2023

    • Author(s)
      S. Yamasaki, N. Koga, M. Zwama, K. Sakurai, R. Nakashima, A. Yamaguchi, K. Nishino
    • Organizer
      9th Symposium on Antimicrobial Resistance in Animals and the Environment (ARAE 2023)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Global analysis of genes regulated by Rof in Salmonella enterica serovar Typhimurium2023

    • Author(s)
      Ryo Tanida, Sohei Nakano, Seiji Yamasaki, Atsushi Taguchi, and Kunihiko Nishino
    • Organizer
      The 26th SANKEN International Symposium
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of Universal Inhibitors of Drug Efflux Pumps to Overcome Multidrug-Resistant Pseudomonas aeruginosa Infections2023

    • Author(s)
      Seiji Yamasaki, Ryosuke Nakashima, Takayoshi Suzuki, and Kunihiko Nishino
    • Organizer
      Gordon Research Conference
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 細菌共存学の発展 ー病原性に寄与する薬剤排出ポンプの阻害剤開発に向けてー2023

    • Author(s)
      山崎聖司
    • Organizer
      日本細菌学会総会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 多剤耐性菌感染症治療を目的とした両親媒性ヘリカルペプチドの開発2022

    • Author(s)
      三澤隆史、平野元春、倉島恵愛、山崎聖司、西野邦彦、出水庸介
    • Organizer
      メディシナルケミストリーシンポジウム
    • Related Report
      2022 Research-status Report
  • [Presentation] 細菌共存学の開拓 -ヒトと病原細菌・腸内細菌との新たな関係の構築-2022

    • Author(s)
      山崎聖司
    • Organizer
      産研学術講演会
    • Related Report
      2022 Research-status Report
  • [Presentation] 新規制御手法の開発による細菌とのより良い共存関係の構築2022

    • Author(s)
      山崎聖司
    • Organizer
      第4回COI 学術交流会
    • Related Report
      2021 Research-status Report
  • [Presentation] MacABの発現はRho依存型ターミネーターを介して、Rofによって調整されている2022

    • Author(s)
      中野草平、山崎聖司、田口厚志、西野邦彦
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Research-status Report
  • [Presentation] MacABの発現はRho依存型ターミネーターを介して、Rofによって調整されている2022

    • Author(s)
      中野草平、山崎聖司、田口厚志、西野邦彦
    • Organizer
      第95回日本細菌学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 細菌とのより良い共存関係の構築2022

    • Author(s)
      山崎聖司
    • Organizer
      第10回大阪大学COIシンポジウム
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 新規抗菌薬セフィデロコル自然抵抗性における緑膿菌薬剤排出ポンプの役割解明2021

    • Author(s)
      井川創太、山崎聖司、森田雄二、西野邦彦
    • Organizer
      第33回 微生物シンポジウム
    • Related Report
      2021 Research-status Report
  • [Presentation] 腸内フローラの改善による人間力活性化メカニズムの解明2021

    • Author(s)
      西野邦彦、山崎聖司、熊ノ郷淳
    • Organizer
      イノベーションジャパン2021(JSTフェア)
    • Related Report
      2021 Research-status Report
  • [Presentation] イオン移動度分光の腸内環境センシングへの応用2021

    • Author(s)
      氏本勝也、向井琢雄、山崎聖司、西野邦彦
    • Organizer
      イノベーションジャパン2021(JSTフェア)
    • Related Report
      2021 Research-status Report
  • [Presentation] 大阪大学拠点における若手活動の振り返り2021

    • Author(s)
      山崎聖司
    • Organizer
      プレ第6回COI2021 会議
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] The increasingly pressing role of RND-type efflux pumps in multidrug resistant pathogens2021

    • Author(s)
      Martijn Zwama, Ryosuke Nakashima, Seiji Yamasaki, Kunihiko Nishino
    • Organizer
      10th imec Handai International Symposium
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 細菌活動のコントロールによる新たな共存関係の構築2021

    • Author(s)
      山崎聖司
    • Organizer
      第3回ファーマラボEXPO
    • Related Report
      2021 Research-status Report
    • Invited
  • [Remarks] researchmap

    • URL

      https://researchmap.jp/yamasakiseiji

    • Related Report
      2023 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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