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A combination strategy of a semisynthetic macrolide, 5-O-mycaminosyltylonolide with polymyxin B nonapeptide for multi-drug resistance P. aeruginosa

The Journal of Antibiotics volume 76, pages 499–501 (2023)Cite this article

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Abstract

The emergence and spread of antimicrobial resistant pathogens continue to threaten our ability to combat several infections. Among them, Pseudomonas aeruginosa (P. aeruginosa) poses a major threat to human health. P. aeruginosa has intrinsic resistance to many antibiotics due to the impermeability of its outer membrane and a resistance-nodulation-cell division type multidrug efflux pump system. Therefore, only limited therapeutic drugs are effective against the pathogen. To address this problem, we have recently discovered an overlooked anti- P. aeruginosa compound, 5-O-mycaminosyltylonolide (OMT) from the Ōmura Natural Compound library using an efflux pump deletion P. aeruginosa mutant strain, YM64. In this report, we aim to demonstrate the promising potential of OMT for as a novel anti- P. aeruginosa compound and performed combination assays of OMT with polymyxin B nonapeptide, an example of a permeabilizing agent, against multi-drug 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. 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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Author notes

  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. A combination strategy of a semisynthetic macrolide, 5-O-mycaminosyltylonolide with polymyxin B nonapeptide for multi-drug resistance P. aeruginosa. J Antibiot 76, 499–501 (2023). https://doi.org/10.1038/s41429-023-00628-9

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  • DOI: https://doi.org/10.1038/s41429-023-00628-9

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