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Characterization of unstudied RND-type multidrug efflux pumps from pathogenic microorganisms

Research Project

Project/Area Number 20K16242
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49050:Bacteriology-related
Research InstitutionOsaka University

Principal Investigator

Zwama Martijn  大阪大学, 産業科学研究所, 特任助教(常勤) (40827052)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsMultidrug resistance / Pathogens / Bacteria / Transporters / Phylogenetics / Evolution / Adaptation / Antibiotics / RND / Multidrug Resistance / MDR / Efflux pumps / AcrB / Transporter
Outline of Research at the Start

Multidrug resistance is a major threat to human health worldwide. With this research we aim to better understand drug resistance on a molecular level, by investigating RND efflux pumps from multiple previously unstudied bacteria. We will test substrate specificity patterns and inhibition efficiencies. We are also interested to see the possible coupling of the pumps with different outer membrane proteins: an area of recent interests for the development of efflux pump inhibitors.

Outline of Final Research Achievements

Multidrug efflux pumps belonging to the RND superfamily from multiple Gram-negative bacteria have been cloned and expressed, and mutations have been introduced after meticulously studying the differences and similarities of hundreds of pumps. The results show interesting novel findings relevant and important to the field of multidrug resistance regarding the function of RND-type multidrug efflux pumps, their evolution, their conservation, and their function. During this research period, we have published research papers (as well as review articles) in multiple peer-reviewed journals.

Academic Significance and Societal Importance of the Research Achievements

We expanded our understanding of multidrug resistance and provided novel insights into the function and adaptation of RND pumps. This has social significance as it contributes to healthcare strategies in combating multidrug resistance and addresses the global health challenge of drug resistance.

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (7 results)

All 2022 2021 2020

All Journal Article (7 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 6 results,  Open Access: 6 results)

  • [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 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inhibitor binding pits analysis of bacterial multidrug efflux transporters for new drug development2022

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

      Precision Medicine

      Volume: 59 Pages: 56-60

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proximal Binding Pocket Arg717 Substitutions in Escherichia coli AcrB Cause Clinically Relevant Divergencies in Resistance Profiles2022

    • Author(s)
      Zwama Martijn、Nishino Kunihiko
    • Journal Title

      Antimicrobial Agents and Chemotherapy

      Volume: 66 Issue: 4

    • DOI

      10.1128/aac.02392-21

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ever-Adapting RND Efflux Pumps in Gram-Negative Multidrug-Resistant Pathogens: A Race against Time2021

    • Author(s)
      Zwama Martijn、Nishino Kunihiko
    • Journal Title

      Antibiotics

      Volume: 10 Issue: 7 Pages: 774-774

    • DOI

      10.3390/antibiotics10070774

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Proximal binding pocket Arg717 substitutions in Escherichia coli AcrB cause clinically relevant divergencies in resistance profiles2021

    • Author(s)
      Zwama Martijn、Nishino Kunihiko
    • Journal Title

      bioRxiv

      Volume: 12.16 Pages: 473095-473095

    • DOI

      10.1101/2021.12.16.473095

    • Related Report
      2021 Research-status Report
    • Open Access / Int'l Joint Research
  • [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
  • [Journal Article] Identification of Genetic Variants via Bacterial Respiration Gas Analysis2020

    • Author(s)
      Koga Naoki、Hosomi Takuro、Zwama Martijn、Jirayupat Chaiyanut、Yanagida Takeshi、Nishino Kunihiko、Yamasaki Seiji
    • Journal Title

      Frontiers in Microbiology

      Volume: 11 Pages: 581571-581571

    • DOI

      10.3389/fmicb.2020.581571

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

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Published: 2020-04-28   Modified: 2024-01-30  

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