Exploring the principles behind antibiotics with limited resistance.

ABSTRACT: Antibiotics that target multiple cellular functions are anticipated to be less prone to bacterial resistance. Here we hypothesize that while dual targeting is crucial, it is not sufficient in preventing resistance. Only those antibiotics that simultaneously target membrane integrity and block another cellular pathway display reduced resistance development. To test the hypothesis, we focus on three antibiotic candidates, POL7306, Tridecaptin M152-P3 and SCH79797, all of which fulfill the above criteria. Here we show that resistance evolution against these antibiotics is limited in ESKAPE pathogens, including Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, while dual-target topoisomerase antibiotics are prone to resistance. We discover several mec

SUBMITTER: Maharramov E 

PROVIDER: S-EPMC11845477 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature