title: Antibacterial activity and therapeutic efficacy of Fl-P(R)P(R)P(L)-5, a cationic amphiphilic polyproline helix, in a mouse model of staphylococcal skin infection.
abstract: The antibacterial activities and therapeutic efficacy of the cationic, unnatural proline-rich peptide Fl-P(R)P(R)P(L)-5 were evaluated against multidrug-resistant Staphylococcus aureus in a mouse model of skin infection. Fl-P(R)P(R)P(L)-5 showed potent activity against all clinical isolates of S. aureus tested, including methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA, respectively). Fl-P(R)P(R)P(L)-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-P(R)P(R)P(L)-5 enhanced wound closure and significantly reduced bacterial load. Finally, 0.5% Fl-P(R)P(R)P(L)-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-P(R)P(R)P(L)-5 in the treatment of staphylococcal skin infections.
authors.affiliation: Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, West Lafayette, IN, USA.
authors.forename: Shankar
authors.initials: S
authors.lastname: Thangamani
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, IN, USA.
authors.forename: Manish
authors.initials: M
authors.lastname: Nepal
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, IN, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Chmielewski
authors.affiliation: Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, West Lafayette, IN, USA.
authors.forename: Mohamed N
authors.initials: MN
authors.lastname: Seleem
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms; D004195:Disease Models, Animal; D005452:Fluoresceins / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D009842:Oligopeptides / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D013207:Staphylococcal Skin Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000254:growth & development; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; C000608795:Fl-P(R)P(R)P(L)-5 peptide; D005452:Fluoresceins; C587672:IL1B protein, mouse; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D009842:Oligopeptides; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse
keywords: Staphylococcus aureus; anti-inflammatory; antimicrobial peptides; biofilms; skin infection