Killing of Staphylococcus aureus persisters by a multitarget natural product chrysomycin A

• DOI: 10.1126/sciadv.adg5995
• Publication Date: 2023-08-04T17:58:23Z
• Authors: Jia Jia; Mingxin Zheng; Chongwen Zhang; Binglei Li; Cai Lu; Yuefan Bai; Qian Tong; Xudong Hang; Yixin Ge; Liping Zeng; Ming Zhao; Fuhang Song; Huawei Zhang; Liang Zhang; Kui Hong; Hongkai Bi
• Keywords: Lipid II; Natural product

Staphylococcus aureus poses a severe public health problem as one of the vital causative agents healthcare- and community-acquired infections. There is globally urgent need for new drugs with novel mode action (MoA) to combat S. biofilms persisters that tolerate antibiotic treatment. We demonstrate benzonaphthopyranone glycoside, chrysomycin A (ChryA), rapid bactericide highly active against persisters, robustly eradicates in vitro, shows sustainable killing efficacy vivo. ChryA was suggested target multiple critical cellular processes. wide range genetic biochemical approaches showed directly binds GlmU DapD, involved biosynthetic pathways cell wall peptidoglycan lysine precursors, respectively, inhibits acetyltransferase activities by competition their mutual substrate acetyl-CoA. Our study provides an effective antimicrobial strategy combining MoAs onto single small molecule treatments persistent