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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 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.

SUBMITTER: Lainson JC 

PROVIDER: S-EPMC5554890 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Synthetic Antibacterial Peptide Exhibits Synergy with Oxacillin against MRSA.

Lainson John C JC   Daly Seth M SM   Triplett Kathleen K   Johnston Stephen Albert SA   Hall Pamela R PR   Diehnelt Chris W CW  

ACS medicinal chemistry letters 20170707 8


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 fl  ...[more]

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