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 Staphylococcus aureus (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, ASU014, composed of a S. aureus binding peptide and a S. aureus inhibitory peptide conjugated to a branched peptide scaffold, which has modest activity against S. aureus but exhibits synergy with oxacillin for MRSA both in vitro and in a MRSA skin infection model. The low concentration of ASU014 and sub-MIC concentration of oxacillin necessary for activity suggest that this molecule is a candidate for future medicinal chemistry optimization.
Original language | English (US) |
---|---|
Pages (from-to) | 853-857 |
Number of pages | 5 |
Journal | ACS Medicinal Chemistry Letters |
Volume | 8 |
Issue number | 8 |
DOIs | |
State | Published - Aug 10 2017 |
Keywords
- MRSA
- antibacterial peptide
- oxacillin
- potentiator
ASJC Scopus subject areas
- Biochemistry
- Drug Discovery
- Organic Chemistry