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Efflux pump inhibitor, phenylalanine-arginine beta-naphthylamide analog potentiates the activity of 5-O-mycaminosyltylonolide for multi-drug resistant Pseudomonas aeruginosa

The Journal of Antibiotics volume 77, pages 331–333 (2024)Cite this article

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Abstract

The emergence and spread of antimicrobial resistance are global threats. Pseudomonas aeruginosa (P. aeruginosa) is responsible for a substantial proportion of this global health issue because of its intrinsic resistance to many antibiotics due to the impermeability of its outer membrane and its multidrug efflux pump systems. Therefore, therapeutic drugs are limited, and the development of new drugs is extremely challenging. As an alternative approach, we focused on a combinational treatment strategy and found that 5-O-mycaminosyltylonolide (OMT) showed potent antibacterial activity against P. aeruginosa in the presence of an efflux pump inhibitor, phenylalanine-arginine beta-naphthylamide (PAβN). In this report, we prepared a PAβN derivative and compared the potentiation activity of OMT by PAβNs against multidrug-resistant P. aeruginosa clinical isolates.

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Acknowledgements

We are grateful to Distinguished Emeritus Professor Satoshi Ōmura (Kitasato University) for his helpful support and valuable suggestions. 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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Author notes

  1. These authors contributed equally: Aoi Kimishima, Masako Honsho, Junsei Terai

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, Junsei Terai, Sota Honma, Hidehito Matsui, Hideaki Hanaki & Yukihiro Asami

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

    Aoi Kimishima, Masako Honsho, Sota Honma, Hidehito Matsui, Hideaki Hanaki & Yukihiro Asami

  3. 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., Honsho, M., Terai, J. et al. Efflux pump inhibitor, phenylalanine-arginine beta-naphthylamide analog potentiates the activity of 5-O-mycaminosyltylonolide for multi-drug resistant Pseudomonas aeruginosa. J Antibiot 77, 331–333 (2024). https://doi.org/10.1038/s41429-024-00713-7

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