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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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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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