Membrane‐active peptide PV 3 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 PV 3 against a MDR isolate of Pseudomonas aeruginosa in a mouse model of burn infection. The structural analysis of PV 3 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 PV 3 occurred at the membrane of bacteria. Peptide PV 3 exhibited superior in vitro anti‐ Pseudomonas activity and killing kinetics as compared with doripenem. A single dose of the topically applied peptide PV 3 (4 ×  MBC , 120 min) was found to be sufficient to eradicate MDR P. 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 PV 3‐associated bactericidal activity, contrary to doripenem. An in‐depth analysis of mouse skin by histopathology revealed that peptide PV 3 (4 ×  MBC ) did not induce any topical skin toxicity. Overall, the data strongly suggest that peptide PV 3 might be a potent candidate antimicrobial agent active on antibiotic‐resistant isolates of pathogenic bacteria.