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

Drug Des Devel Ther. 2015 Oct 22;9:5749-54. doi: 10.2147/DDDT.S94505. eCollection 2015.


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.

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

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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*
  • Methicillin-Resistant Staphylococcus aureus / growth & development
  • Methicillin-Resistant Staphylococcus aureus / pathogenicity
  • Oligopeptides / pharmacology*
  • Peptides / pharmacology*
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / microbiology
  • Staphylococcal Skin Infections / drug therapy*
  • Staphylococcal Skin Infections / metabolism
  • Staphylococcal Skin Infections / microbiology
  • Staphylococcus epidermidis / drug effects
  • Staphylococcus epidermidis / growth & development
  • Tumor Necrosis Factor-alpha / metabolism


  • 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