De novo-derived cationic antimicrobial peptide activity in a murine model of Pseudomonas aeruginosa bacteraemia

J Antimicrob Chemother. 2007 Sep;60(3):669-72. doi: 10.1093/jac/dkm253. Epub 2007 Jul 10.

Abstract

Objectives: We describe the antimicrobial activity against Pseudomonas aeruginosa of the de novo-derived antimicrobial peptide WLBU2 in an animal model of infection.

Methods: For this study, an intravenous (iv) model of P. aeruginosa infection was established. The minimum lethal murine dose of P. aeruginosa strain PA01 was determined to be 3 x 10(7) cfu when bacteria were administered iv. Increasing concentrations of WLBU2 were instilled either prior to or following PA01 septic exposure.

Results: For the mice given peptide post-bacterial infection, in the 1 mg/kg group, nine of nine animals died because of Pseudomonas sepsis; in the 3 mg/kg group, only one of nine succumbed to infection and in the 4 mg/kg group, all mice were protected (P < 0.0001). Similar results were obtained when WLBU2 was given 1 h prior to Pseudomonas infection.

Conclusions: Although the therapeutic window in this model is narrow, the results nonetheless provide encouraging evidence for WLBU2 as a potential prophylactic or treatment of bacterial infection.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antimicrobial Cationic Peptides / isolation & purification
  • Antimicrobial Cationic Peptides / pharmacology
  • Antimicrobial Cationic Peptides / therapeutic use*
  • Bacteremia / drug therapy*
  • Bacteremia / microbiology
  • Disease Progression
  • Mice
  • Molecular Sequence Data
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas Infections / microbiology
  • Sepsis / microbiology
  • Sepsis / prevention & control
  • Survival

Substances

  • Antimicrobial Cationic Peptides
  • WLBU2 peptide