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: Shankar Thangamani, Manish Nepal, Jean Chmielewski, Mohamed N Seleem
• Journal: Drug design, development and therapy (Drug Des Devel Ther) Vol. 9 Pg. 5749-54 ( 2015) ISSN: 1177-8881 [Electronic] New Zealand
• PMID: 26543355 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anti-Bacterial Agents
• Fl-P(R)P(R)P(L)-5 peptide
• Fluoresceins
• IL1B protein, mouse
• Inflammation Mediators
• Interleukin-1beta
• Interleukin-6
• Oligopeptides
• Peptides
• Tumor Necrosis Factor-alpha
• interleukin-6, mouse

Topics

• Animals
• Anti-Bacterial Agents (pharmacology)
• Biofilms
• Disease Models, Animal
• Fluoresceins (pharmacology)
• Inflammation Mediators (metabolism)
• Interleukin-1beta (metabolism)
• Interleukin-6 (metabolism)
• Methicillin-Resistant Staphylococcus aureus (drug effects, growth & development, pathogenicity)
• Oligopeptides (pharmacology)
• Peptides (pharmacology)
• Skin (drug effects, metabolism, microbiology)
• Staphylococcal Skin Infections (drug therapy, metabolism, microbiology)
• Staphylococcus epidermidis (drug effects, growth & development)
• Tumor Necrosis Factor-alpha (metabolism)