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

Berthony Deslouches, Ivan A. Gonzalez, Dilhari DeAlmeida, Kazi Islam, Chad Steele, Ronald C. Montelaro, Timothy A. Mietzner

Research output: Contribution to journalArticle

43 Scopus citations

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 × 107 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.

Original languageEnglish (US)
Pages (from-to)669-672
Number of pages4
JournalJournal of Antimicrobial Chemotherapy
Volume60
Issue number3
DOIs
StatePublished - Sep 2007

Keywords

  • Antimicrobial peptide
  • Sepsis
  • WLBU2

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology

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