Teixobactin kills bacteria by a two-pronged attack on the cell envelope.

ABSTRACT: Antibiotics that use novel mechanisms are needed to combat antimicrobial resistance^1-3. Teixobactin⁴ represents a new class of antibiotics with a unique chemical scaffold and lack of detectable resistance. Teixobactin targets lipid II, a precursor of peptidoglycan⁵. Here we unravel the mechanism of teixobactin at the atomic level using a combination of solid-state NMR, microscopy, in vivo assays and molecular dynamics simulations. The unique enduracididine C-terminal headgroup of teixobactin specifically binds to the pyrophosphate-sugar moiety of lipid II, whereas the N terminus coordinates the pyrophosphate of another lipid II molecule. This configuration favours the formation of a β-sheet of teixobactins bound to the target, creating a supramolecular fibr

SUBMITTER: Shukla R 

PROVIDER: S-EPMC9365693 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature