Membrane‐active peptide PV3 efficiently eradicates multidrug‐resistant Pseudomonas aeruginosa in a mouse model of burn infection

The aim of this study was to evaluate the topical bactericidal activity of peptide PV3 against a MDR isolate of Pseudomonas aeruginosa in a mouse model of burn infection. The structural analysis of PV3 by circular dichroism spectroscopy indicated a low peptide helical content in water, whereas a high helical content was observed in the presence of the more hydrophobic 50% (v/v) trifluoroethanol/water buffer. A confocal microscopy analysis indicated that the main action of PV3 occurred at the membrane of bacteria. Peptide PV3 exhibited superior in vitro anti‐Pseudomonas activity and killing kinetics as compared with doripenem. A single dose of the topically applied peptide PV3 (4 × MBC, 120 min) was found to be sufficient to eradicate MDRP. aeruginosa in a bacterially infected mouse burn wound model, whereas doripenem (4 × MBC) failed to eradicate the initial inoculum. This indicates a potent and fast PV3‐associated bactericidal activity, contrary to doripenem. An in‐depth analysis of mouse skin by histopathology revealed that peptide PV3 (4 × MBC) did not induce any topical skin toxicity. Overall, the data strongly suggest that peptide PV3 might be a potent candidate antimicrobial agent active on antibiotic‐resistant isolates of pathogenic bacteria.