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Antibacterial activity and therapeutic efficacy of Fl-PRPRPL-5, a cationic amphiphilic polyproline helix, in a mouse model of staphylococcal skin infection

Authors Thangamani S, Nepal M, Chmielewski J, Seleem M

Received 15 August 2015

Accepted for publication 16 September 2015

Published 22 October 2015 Volume 2015:9 Pages 5749—5754

DOI https://doi.org/10.2147/DDDT.S94505

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Wei Duan


Shankar Thangamani,1 Manish Nepal,2 Jean Chmielewski,2 Mohamed N Seleem1

1Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, West Lafayette, IN, USA; 2Department of Chemistry, Purdue University, West Lafayette, IN, USA

Abstract: The 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.

Keywords: antimicrobial peptides, Staphylococcus aureus, biofilms, anti-inflammatory, skin infection

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