Repurposing bunamidine hydrochloride as a potent antimicrobial agent targeting vancomycin-resistant <i>Enterococcus</i> membranes

The global rise of vancomycin-resistant enterococci (VRE) poses serious challenges in clinical treatment due to limited therapeutic options and rapid resistance development. This study identifies bunamidine hydrochloride (BUN), a previously approved antiparasitic agent, as a potent membrane-targeting antimicrobial with rapid bactericidal activity against both planktonic and biofilm-associated VRE. By selectively interacting with bacterial phosphatidylglycerol, BUN disrupts membrane integrity and inhibits persister cells, while maintaining low cytotoxicity and high <i>in vivo</i> efficacy in murine infection models. Our findings highlight the potential of drug repurposing strategies to accelerate the discovery of effective antibiotics and provide a promising candidate for future clinical management of multidrug-resistant bacterial infections.