Discovery of antibacterial diketones against gram-positive bacteria

文献类型： 外文期刊

第一作者： Li, Qian

作者： Li, Qian;Zhu, Kui;Feng, Hanzhong;Xiang, Yun;He, Yong-Xing;Tian, Qiong;Wang, Xiaolei;Tian, Qiong;Wang, Xiaolei;He, Yong-Xing

作者机构：

期刊名称：CELL CHEMICAL BIOLOGY （ 影响因子：7.2； 五年影响因子：8.7 ）

ISSN： 2451-9456

年卷期： 2024 年 31 卷 11 期

页码：

收录情况： SCI

摘要： The rapid rise of antibiotic resistance calls for the discovery of new antibiotics with distinct antibacterial mechanisms. New target mining is indispensable for developing antibiotics. Plant-microbial antibiotics are appealing to underexplored sources due to a dearth of comprehensive understanding of antibacterial activity and the excavation of new targets. Here, a series of phloroglucinol derivatives of plant-root-associated Pseudomonas fluorescens were synthesized for structure-activity relationship analysis. Notably, 2,4-diproylphloroglucinol (DPPG) displayed efficient bactericidal activity against a wide range of gram-positive bacteria. Importantly, mechanistic study exhibits that DPPG binds to type II NADH dehydrogenase (NDH-2), an essential enzyme catalyzing the transfer of electrons from NADH to quinones in the electron transport chain (ETC), blocking electron transfer in S. aureus. Last, we validated the efficacy of DPPG in vivo through animal infection models. Our findings not only provide a distinct antibiotic lead to treat multidrug resistant pathogens but also identify a promising antibacterial target.

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