Staphylococcus aureus-targeting peptide/surfactant assemblies for antibacterial therapy

To address the challenge from microbial resistance, this work developed a surfactant with 18-carbon single hydrocarbon chain and multi-amine head groups (C18N3). After assembling with Staphylococcus aureus-targeting peptide (CARG), the obtained C18N3/CARG assemblies exhibited excellent antimicrobial activities against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus in vitro and in vivo, in which the targeting peptide CARG bonded specifically to Staphylococcus aureus and C18N3 killed bacteria with a mechanism of membrane disruption. Importantly, C18N3 could also work as a beta-lactamase inhibitor to overcome the bacterial resistance to beta-lactam antibiotics through noncompetitive inhibition. The combination of beta-lactam antibiotic and C18N3/CARG assemblies more effectively suppressed methicillin-resistant Staphylococcus aureus in vitro and in vivo relative to equivalent dose of free antibiotic or C18N3. Thus, the antibacterial platform of antibiotic carrying surfactant assemblies bearing bacteria-targeted peptides, in which C18N3 performed dual function, antibacterial agent and beta-lactamase inhibitor, may help fight against the difficult-to-treat infections.