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2021 年度 実施状況報告書

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

研究課題

研究課題/領域番号 20K16242
研究機関大阪大学

研究代表者

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

研究期間 (年度) 2020-04-01 – 2023-03-31
キーワードRND / Transporter / Multidrug Resistance / MDR / AcrB / Evolution
研究実績の概要

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. In this fiscal year, we were able to publish two articles, a review and a research article as first author and corresponding author, and one as a contributing author. In the review article, I wrote an extensive overview of a comparison of hundreds of pumps, and explored useful information about the conservation and differences between all these pumps. In the research article, I used the data obtained from the review article to explore upcoming mutations in clinical strains in Nepal, India, Sri Lanka and Pakistan, showing that these mutations cause significantly increased resistance in certain antibiotics, while importantly decreasing resistance to other drugs. In addition, the main results from the past two Fiscal Years funded by this project (multiple unstudied pumps) are heading towards completion and some (probably at least three) articles are close to being prepared.

現在までの達成度 (区分)
現在までの達成度 (区分)

1: 当初の計画以上に進展している

理由

All pumps cloned are active and multiple important results have been obtained, more than anticipated. Some published, while the main findings most likely in the coming FY.

今後の研究の推進方策

Continue with the research as planned and perform experiments based on the positive procedures and results obtain in FY2020-2021. In this FY2022, focus on the last experiments before publication.

次年度使用額が生じた理由

Slight delay in research due to COVID-19, the budget will be used to continue the planned research as in the proposal efficiently. Also due to other budget limitations, the carry-over is needed and wished for to effectively continue the study of the main project. However, most part of the carry-over amount (around 190k of the 260k) is already used for a plasmid order from the end of FY2021, which was delivered (and paid for) in the beginning of FY2022.

  • 研究成果

    (4件)

すべて 2022 2021

すべて 雑誌論文 (4件) (うち国際共著 4件、 査読あり 3件、 オープンアクセス 4件)

  • [雑誌論文] Proximal Binding Pocket Arg717 Substitutions in Escherichia coli AcrB Cause Clinically Relevant Divergencies in Resistance Profiles2022

    • 著者名/発表者名
      Zwama Martijn、Nishino Kunihiko
    • 雑誌名

      Antimicrobial Agents and Chemotherapy

      巻: 66 ページ: e02392-21

    • DOI

      10.1128/aac.02392-21

    • 査読あり / オープンアクセス / 国際共著
  • [雑誌論文] Ever-Adapting RND Efflux Pumps in Gram-Negative Multidrug-Resistant Pathogens: A Race against Time2021

    • 著者名/発表者名
      Zwama Martijn、Nishino Kunihiko
    • 雑誌名

      Antibiotics

      巻: 10 ページ: 774~774

    • DOI

      10.3390/antibiotics10070774

    • 査読あり / オープンアクセス / 国際共著
  • [雑誌論文] Proximal binding pocket Arg717 substitutions in Escherichia coli AcrB cause clinically relevant divergencies in resistance profiles2021

    • 著者名/発表者名
      Zwama Martijn、Nishino Kunihiko
    • 雑誌名

      bioRxiv

      巻: 12.16 ページ: 473095

    • DOI

      10.1101/2021.12.16.473095

    • オープンアクセス / 国際共著
  • [雑誌論文] Function and Inhibitory Mechanisms of Multidrug Efflux Pumps2021

    • 著者名/発表者名
      Nishino Kunihiko、Yamasaki Seiji、Nakashima Ryosuke、Zwama Martijn、Hayashi-Nishino Mitsuko
    • 雑誌名

      Frontiers in Microbiology

      巻: 12 ページ: 737288

    • DOI

      10.3389/fmicb.2021.737288

    • 査読あり / オープンアクセス / 国際共著

URL: 

公開日: 2022-12-28  

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