Synthetic Antibacterial Peptide Exhibits Synergy with Oxacillin against MRSA

John C. Lainson, Seth M. Daly, Kathleen Triplett, Stephen Johnston, Pamela R. Hall, Chris Diehnelt

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


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 languageEnglish (US)
Pages (from-to)853-857
Number of pages5
JournalACS Medicinal Chemistry Letters
Issue number8
StatePublished - Aug 10 2017


  • MRSA
  • antibacterial peptide
  • oxacillin
  • potentiator

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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