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

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

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