Thangamani, ShankarNepal, ManishChmielewski, JeanSeleem, Mohamed N.2020-09-212020-09-212015-01-011177-8881dddt-9-5749 (PII)http://hdl.handle.net/10919/100018The antibacterial activities and therapeutic efficacy of the cationic, unnatural proline-rich peptide Fl-PRPRPL-5 were evaluated against multidrug-resistant Staphylococcus aureus in a mouse model of skin infection. Fl-PRPRPL-5 showed potent activity against all clinical isolates of S. aureus tested, including methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA, respectively). Fl-PRPRPL-5 was also superior in clearing established in vitro biofilms of S. aureus and Staphylococcus epidermidis, compared with the established antimicrobials mupirocin and vancomycin. Additionally, topical treatment of an MRSA-infected wound with Fl-PRPRPL-5 enhanced wound closure and significantly reduced bacterial load. Finally, 0.5% Fl-PRPRPL-5 significantly reduced the levels of the inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) in wounds induced by MRSA skin infection. In conclusion, the results of this study suggest the potential application of Fl-PRPRPL-5 in the treatment of staphylococcal skin infections.Pages 5749-57546 page(s)Electronic-eCollectionapplication/pdfenCreative Commons Attribution-NonCommercial 4.0 InternationalChemistry, MedicinalPharmacology & Pharmacyantimicrobial peptidesStaphylococcus aureusbiofilmsanti-inflammatoryskin infectionAUREUSPEPTIDESCOMPLICATIONSINFLAMMATIONBACTERIABIOFILMALPHARISK1115 Pharmacology and Pharmaceutical SciencesSkinAnimalsBiofilmsStaphylococcus epidermidisStaphylococcal Skin InfectionsDisease Models, AnimalFluoresceinsPeptidesTumor Necrosis Factor-alphaOligopeptidesInflammation MediatorsInterleukin-6Anti-Bacterial AgentsInterleukin-1betaMethicillin-Resistant Staphylococcus aureusAntibacterial activity and therapeutic efficacy of Fl-PRPRPL-5, a cationic amphiphilic polyproline helix, in a mouse model of staphylococcal skin infectionArticle - Refereed2020-09-21Drug Design Development and Therapyhttps://doi.org/10.2147/DDDT.S945059Seleem, Mohamed [0000-0003-0939-0458]26543355 (pubmed)1177-8881