Novel short-lived, broadly acting peptide-polyene bacteriocin from nasal microbiome shapes bacterial communities and eliminates Staphylococcus aureus. Staphylococcus competition

Antagonistic bacterial interactions often rely on antimicrobial bacteriocins, which attack only a narrow range of target bacteria. However, rapidly changing microbiomes may promote antimicrobials with broader activity. We report here a new type of antimicrobial, epifadin, produced by nasal Staphylococcus epidermidis. It encompasses two non-ribosomally synthesized peptide moieties and a polyketide linker in an unprecedented architecture. Epifadin combines a wide antimicrobial target spectrum with an extraordinarily short life span. It is surprisingly unstable under in vivo-like, ambient conditions, presumably as a means to limit collateral damage of mutualistic interactions by epifadin-producing S. epidermidis cells. However, Staphylococcus aureus is effectively eliminated by epifadin-producing S. epidermidis during co-cultivation in vitro and in vivo indicating that epifadin-producing commensals could help to prevent nasal S. aureus carriage. Our study describes a new microbiome-derived antimicrobial class and suggests that limiting the half-life of an antimicrobial may help to balance its beneficial and detrimental activities against other bacteria.