The last resort antibiotic daptomycin exhibits two independent antibacterial mechanisms of action.

ABSTRACT: Daptomycin is a lipopeptide antibiotic, commonly used as last resort treatment against multidrug resistant Gram-positive pathogens. Despite its clinical success, the mechanism through which daptomycin exerts its antibacterial properties has remained controversial. Much of the debate is focused around daptomycin's ability to depolarise the cytoplasmic membrane, potential formation of large membrane pores, and its more recently discovered capability to inhibit cell wall synthesis and disturb membrane lipid domain organisation through interactions with cell wall precursor lipids. Here we show that, rather than representing different facets of a single underlying activity, daptomycin exhibits two independent antibacterial mechanisms of action: (i) targeting of cell wall precursor lipids that l

SUBMITTER: Buttress JA 

PROVIDER: S-EPMC12645038 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature