A new antibiotic from an uncultured bacterium binds to an immutable target.

ABSTRACT: Antimicrobial resistance is a leading mortality factor worldwide. Here we report the discovery of clovibactin, a new antibiotic, isolated from uncultured soil bacteria. Clovibactin efficiently kills drug-resistant bacterial pathogens without detectable resistance. Using biochemical assays, solid-state NMR, and atomic force microscopy, we dissect its mode of action. Clovibactin blocks cell wall synthesis by targeting pyrophosphate of multiple essential peptidoglycan precursors (C ₅₅ PP, Lipid II, Lipid _WTA ). Clovibactin uses an unusual hydrophobic interface to tightly wrap around pyrophosphate, but bypasses the variable structural elements of precursors, accounting for the lack of resistance. Selective and efficient target binding is achieved by the irreversible seque

SUBMITTER: Shukla R 

PROVIDER: S-EPMC10245560 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature