Elimination of Antibiotic Resistant Surgical Implant Biofilms Using an Engineered Cationic Amphipathic Peptide WLBU2

Sci Rep. 2017 Dec 22;7(1):18098. doi: 10.1038/s41598-017-17780-6.

Abstract

Antibiotics are unable to remove biofilms from surgical implants. This high antibiotic tolerance is related to bacterial persisters, a sub-population of bacteria phenotypically tolerant to antibiotics secondary to a reduced metabolic state. WLBU2 is an engineered cationic amphipathic peptide designed to maximize antimicrobial activity with minimal mammalian cell toxicity. The objective of this study was to test the ability of WLBU2 to remove Staphylococcus aureus surgical implant biofilms. WLBU2 effectively treated S. aureus biofilms formed by a variety of clinical MSSA and MRSA strains and created culture-negative implants in the in vitro biofilm model. Blocking bacterial metabolism by inhibiting oxidative phosphorylation did not affect WLBU2 killing compared to decreased killing by cefazolin. In the surgical implant infection animal model, WLBU2 decreased biofilm mass as compared to control, untreated samples. WLBU2 could rapidly eliminate implants in vitro and had sufficient efficacy in vivo with minimal systemic toxicity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Antimicrobial Cationic Peptides / pharmacology*
  • Antimicrobial Cationic Peptides / therapeutic use
  • Biofilms / drug effects*
  • Disease Models, Animal
  • Mice
  • Oxidative Phosphorylation / drug effects
  • Prosthesis-Related Infections / drug therapy*
  • Staphylococcus aureus / drug effects*

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • WLBU2 peptide