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JAC Advance Access published online on July 10, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm253
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

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

Berthony Deslouches1,{dagger}, Ivan A. Gonzalez2,{dagger}, Dilhari DeAlmeida1, Kazi Islam1, Chad Steele2, Ronald C. Montelaro1 and Timothy A. Mietzner1,*

1 Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA 2 Department of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, PA 15261, USA

Received 17 May 2007; returned 31 May 2007; revised 8 June 2007; accepted 15 June 2007

* Corresponding author. Tel: +1-412-648-9244; Fax: +1-412-624-1401; E-mail: mietzner{at}pitt.edu

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 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.

Key Words: antimicrobial peptide , WLBU2 , sepsis

{dagger} These authors contributed equally to this paper.


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