Repurposing Benzbromarone as an Antibacterial Agent\nagainst Gram-Positive Bacteria

The\nrise of antibiotic-resistant Gram-positive pathogens, particularly\nmethicillin-resistant <i>Staphylococcus aureus</i> (MRSA),\npresents a significant challenge in clinical settings. There is a\ncritical need for new antibacterial agents to combat these resistant\nstrains. Our study reveals that the uricosuric drug Benzbromarone\n(Benz) exhibits potent antibacterial activity against Gram-positive\npathogens, with minimum inhibitory concentrations (MICs) ranging from\n8 to 32 μg/mL and minimum bactericidal concentrations (MBCs)\nranging from 32 to 128 μg/mL against clinical isolates of <i>S. aureus</i>, <i>S. epidermidis</i>, <i>Enterococcus\nfaecalis</i>, and <i>Streptococcus agalactiae</i>.\nFurthermore, Benz significantly inhibits biofilm formation at subinhibitory\nconcentrations and eradicates mature biofilms at higher concentrations.\nBenz also suppresses the hemolytic activity of <i>S. aureus</i>, indicating its potential to reduce virulence. Proteomic and <i>in vitro</i> induced resistance analyses indicate that Benz\ninhibits protein synthesis and turnover. Additionally, Benz induces\nmembrane depolarization and increases membrane permeability, likely\nby targeting the membrane phospholipid phosphatidylethanolamine (PE).\nIn the mouse wound infection model, Benz promotes wound healing and\nsignificantly reduces bacterial load. These findings suggest that\nBenz is a promising candidate for developing new antibacterial therapies\nagainst Gram-positive bacterial infections.