A Hybrid Antimicrobial Peptide Targeting Staphylococcus aureus with a Dual Function of Inhibiting Quorum Sensing Signaling and an Antibacterial Effect

Community-associated methicillin-resistant Staphylococcus aureus (MRSA) is now a major cause of bacterial infection. Antivirulence therapy does not stimulate evolution of a pathogen toward a resistant phenotype, providing a novel method to treat infectious diseases. Here, we used a cyclic peptide of CP7, an AIP-III variant that specifically inhibited the virulence and biofilm formation of Staphylococcus aureus (S. aureus) in a nonbiocidal manner, to conjugate with a broad-spectrum antimicrobial peptide (AMP) via two N-termini to obtain a hybrid AMP called CP7-FP13-2. This peptide not only specifically inhibited the production of virulence of S. aureus at low micromolar concentrations but also killed S. aureus, including MRSA, by disrupting the integrity of the bacterial cell membrane. In addition, CP7-FP13-2 inhibited the formation of the S. aureus biofilm and showed good antimicrobial efficacy against the S. aureus-infected Kunming mice model. Therefore, this study provides a promising strategy against the resistance and virulence of S. aureus.