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Study of clinically over-expressed and chimeric RND multidrug efflux pumps from Acinetobacter baumannii and Pseudomonas aeruginosa

研究課題

研究課題/領域番号 23K14346
研究種目

若手研究

配分区分基金
審査区分 小区分47030:薬系衛生および生物化学関連
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, 特任准教授(常勤) (40827052)

研究期間 (年度) 2023-04-01 – 2025-03-31
研究課題ステータス 交付 (2023年度)
配分額 *注記
4,680千円 (直接経費: 3,600千円、間接経費: 1,080千円)
2024年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
2023年度: 3,250千円 (直接経費: 2,500千円、間接経費: 750千円)
キーワードRND / Transporter / Multidrug Resistance / MDR / Efflux Pump / Pathogens
研究開始時の研究の概要

Summary: Study RND-type efflux pumps in A. baumannii and P. aeruginosa.

Outline: Investigate three efflux pump complexes in A. baumannii, test inhibitors, sequence for substitutions, and create knockouts and chimeras. Compare P. aeruginosa's MexD and MexF pumps, create chimera proteins, and express pumps in knockouts to test MIC spectra, inhibition, and stability. Create AdeABC, AdeFGH, and AdeIJK knockouts for Japanese isolates. Transform plasmids to compare substrate specificity and inhibitors. Perform MIC experiments and export assays with efflux pump inhibitors.

研究実績の概要

One of the leading causes of clinical multidrug-resistant (MDR) bacterial hospital isolates is the over-expression of multidrug efflux pumps belonging to the Resistance-Nodulation-cell Division (RND) protein superfamily. We aimed to understand the roles of efflux pumps in clinical isolates to MDR and also study less-studied clinically relevant pumps. During the first fiscal year of this research project, we started the first cloning of RND-type efflux pumps for this project and created active pumps. The results show interesting, novel findings that are relevant and important to the field of multidrug resistance. The preliminary results were very interesting, and we are currently continuing to investigate the phenotypes to help us understand multidrug resistance caused by the RND-type efflux pumps of P. aeruginosa, E. coli, and A. baumannii. Gene expression analysis was also performed, which gave us detailed information about the resistance factors in the resistant bacteria. In this fiscal year, we were also able to publish three papers, including drafting multiple manuscripts and laying the groundwork for additional research and publications in the near future, likely for the next fiscal year.

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

The research went smoothly because there were no problems with cloning, and experimental results showed interesting preliminary results already.

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.

報告書

(1件)
  • 2023 実施状況報告書
  • 研究成果

    (3件)

すべて 2024 2023

すべて 雑誌論文 (3件) (うち国際共著 1件、 査読あり 1件、 オープンアクセス 1件)

  • [雑誌論文] Development of a bacterial release compound assay for prevention and early detection of bacteria-derived diseases2024

    • 著者名/発表者名
      S. Yamasaki, N. Koga, T. Hosomi, M. Zwama, C. Jirayupa, T. Yanagida, K. Nishino
    • 雑誌名

      Medical Science Digest

      巻: 50 ページ: 41-43

    • 関連する報告書
      2023 実施状況報告書
  • [雑誌論文] Comprehensive analysis of the binding site for efflux transporter inhibitors in Pseudomonas aeruginosa2023

    • 著者名/発表者名
      Seiji Yamasaki, Martijn Zwama, Naoki Koga, Keisuke Sakurai, Ryosuke Nakashima, Akihito Yamaguchi, Kunihiko Nishino
    • 雑誌名

      Bio Clinica

      巻: 38 ページ: 74-78

    • 関連する報告書
      2023 実施状況報告書
  • [雑誌論文] Drug resistance and physiological roles of RND multidrug efflux pumps in Salmonella enterica, Escherichia coli and Pseudomonas aeruginosa2023

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

      Microbiology

      巻: 169 号: 6 ページ: 001322-001322

    • DOI

      10.1099/mic.0.001322

    • 関連する報告書
      2023 実施状況報告書
    • 査読あり / オープンアクセス / 国際共著

URL: 

公開日: 2023-04-13   更新日: 2024-12-25  

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