Kimishima Aoi, Sakai Kazunari, Honsho Masako, Wasuwanich Paul, Matsui Hidehito, Watanabe Yoshihiro, Iwatsuki Masato, Sunazuka Toshiaki, Arima Naoaki, Abe Kazutoyo, Hanaki Hideaki, Asami Yukihiro
Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
Ōmura Satoshi Memorial Institute, Kitasato University, Tokyo, 108-8641, Japan.
J Antibiot (Tokyo). 2023 May;76(5):301-303. doi: 10.1038/s41429-023-00607-0. Epub 2023 Mar 24.
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.
抗生素耐药性是一个严重的全球性问题。铜绿假单胞菌是对人类健康构成重大威胁的病原体。然而，耐药-结瘤-细胞分裂型多药外排泵系统保护铜绿假单胞菌免受多种抗生素的影响。因此，可用的治疗药物有限。在这方面，我们使用外排泵缺失的铜绿假单胞菌突变株YM64从大村天然化合物库中筛选被忽视的抗铜绿假单胞菌化合物，这使我们发现了一种半合成大环内酯类化合物5-O- mycaminosyltylonolide，其对标准实验室适应菌株PAO1的抗铜绿假单胞菌活性通过外排泵抑制剂苯丙氨酸-精氨酸β-萘酰胺得到增强。
