Synthetic Antibacterial Peptide Exhibits Synergy with Oxacillin against MRSA

Abstract

One proposed solution to the crisis of antimicrobial resistant (AMR) infections is the development of molecules that potentiate the activity of antibiotics for AMR bacteria, such as methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). Rather than develop broad spectrum compounds, we developed a peptide that could potentiate the activity of a narrow spectrum antibiotic, oxacillin. In this way, the combination treatment could narrowly target the resistant pathogen and limit impact on host flora. We developed a peptide, <b>ASU014</b>, composed of a <i>S. aureus</i> binding peptide and a <i>S. aureus</i> inhibitory peptide conjugated to a branched peptide scaffold, which has modest activity against <i>S. aureus</i> but exhibits synergy with oxacillin for MRSA both <i>in vitro</i> and in a MRSA skin infection model. The low concentration of <b>ASU014</b> and sub-MIC concentration of oxacillin necessary for activity suggest that this molecule is a candidate for future medicinal chemistry optimization.