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An efflux pump deletion mutant enabling the discovery of a macrolide as an overlooked anti-P. aeruginosa active compound

The Journal of Antibiotics volume 76, pages 301–303 (2023)Cite this article

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Abstract

Antimicrobial resistance is a serious, worldwide problem. Pseudomonas aeruginosa (P. aeruginosa) is the pathogen that poses a major threat to human health. However, resistance-nodulation-cell division type multidrug efflux pump systems defend P. aeruginosa from many antibiotics. Therefore, only limited therapeutic drugs are available. In this regard, we screened overlooked anti- P. aeruginosa compounds from the Ōmura Natural Compound library using an efflux pump deletion P. aeruginosa mutant strain, YM64, which led us to find a semisynthetic macrolide, 5-O-mycaminosyltylonolide, whose anti- P. aeruginosa activity against a standard laboratory adapted strain, PAO1, was enhanced by an efflux pump inhibitor, phenylalanine-arginine beta-naphthylamide.

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Acknowledgements

We are grateful to Distinguished Emeritus Professor Satoshi Ōmura (Kitasato University) for his helpful support and valuable suggestions. We thank to Koichi Shiraishi, and Souhei Tanabe (Kowa Company) for valuable advice. This study was partially supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS), the Japan Agency for Medical Research & Development (AMED) under Grant Number JP21am0101096 and JP22ama121035.

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  1. These authors contributed equally: Aoi Kimishima, Kazunari Sakai, Masako Honsho

Authors and Affiliations

  1. Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan

    Aoi Kimishima, Masako Honsho, Hidehito Matsui, Yoshihiro Watanabe, Masato Iwatsuki, Toshiaki Sunazuka, Hideaki Hanaki & Yukihiro Asami

  2. Ōmura Satoshi Memorial Institute, Kitasato University, Tokyo, 108-8641, Japan

    Aoi Kimishima, Masako Honsho, Hidehito Matsui, Yoshihiro Watanabe, Masato Iwatsuki, Toshiaki Sunazuka, Hideaki Hanaki & Yukihiro Asami

  3. Research Management Department, Kowa Company LTD., 4-13-3 Nihonbashi-honcho, Chuo-ku, Tokyo, 103-8433, Japan

    Kazunari Sakai, Naoaki Arima, Kazutoyo Abe & Hideaki Hanaki

  4. University of Florida College of Medicine, Gainesville, FL, USA

    Paul Wasuwanich

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  1. Aoi Kimishima
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Correspondence to Yukihiro Asami.

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Kimishima, A., Sakai, K., Honsho, M. et al. An efflux pump deletion mutant enabling the discovery of a macrolide as an overlooked anti-P. aeruginosa active compound. J Antibiot 76, 301–303 (2023). https://doi.org/10.1038/s41429-023-00607-0

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  • DOI: https://doi.org/10.1038/s41429-023-00607-0

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