Marine antimicrobial peptide scyreprocin exhibits therapeutic potential against multidrug-resistant bacteria in wound and lung infections with low resistance.

Antibiotic resistance, driven by multidrug-resistant (MDR) pathogens, poses a major global health threat. Antimicrobial peptides (AMPs) have garnered significant attention as promising therapeutic agents for combating MDR bacteria. Here, we demonstrate the potent antimicrobial activity of scyreprocin against MDR strains, including Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Notably, scyreprocin eradicated the tested strains without inducing drug resistance, inhibited biofilm formation, and eliminated persister cells. In terms of in vivo efficacy, scyreprocin displayed excellent activity against S. aureus and K. pneumoniae in a full-thickness wound infection model. Furthermore, administration of scyreprocin reduced bacterial burden in a K. pneumoniae lung infection model, thereby attenuating the pulmonary inflammatory response. Crucially, under cumulative administration of 25 mg/kg for 5 days, scyreprocin treatment via intravenous injection exerted no in vivo toxicity to mice. Mechanistic studies indicated that scyreprocin triggered membrane damage by causing rapid membrane permeability and leakage. Taken together, the marine-sourced scyreprocin demonstrates effective therapeutic potential for treating infections caused by drug-resistant pathogens.