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

Abstract

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.

The activity and action mechanism of novel short selective LL‐37‐derived anticancer peptides against clinical isolates of Escherichia coli

“…In agreement with the current study, previous reports revealed rapid bactericidal activities of synthetic AMPs over tested antibiotics . It is worthwhile noting that a faster killing action of AMPs has unique advantages over traditional antibiotics such as limiting spread of infection, diminishing the likelihood of developing drug resistance, and reducing treatment duration …”

“…These fascinating peptides usually maintain common physicochemical characteristics. In general, AMPs consist of less than 50 amino acid residues, exhibit a positive net charge, and display an amphipathic nature . These characteristics are believed to be crucial for antimicrobial activity of AMPs .…”

“…In general, AMPs consist of less than 50 amino acid residues, exhibit a positive net charge, and display an amphipathic nature . These characteristics are believed to be crucial for antimicrobial activity of AMPs . In contrast to conventional antibiotics targeting specific biosynthetic pathways such as protein and cell wall synthesis, AMPs can destabilize the physical integrity of the bacterial membrane, thereby circumventing classical mechanisms of drug resistance …”

Multivalent Glycosheets for Double Light–Driven Therapy of Multidrug‐Resistant Bacteria on Wounds

“…It is estimated that P. aeruginosa infection accounts for a higher mortality rate than burn shock and hypovolemia in burn care units. Considering the lethal effects of wound infection with multidrug‐resistant P. aeruginosa , the lack of effective therapeutic regimes as well as the frequency of bacterial infection in developing countries, novel, effective, and economic antimicrobial agents are urgently needed …”

Near-Infrared Fluorescent Peptides with High Tumor Selectivity: Novel Probes for Image-Guided Surgical Resection of Orthotopic Glioma

“…These peptides strongly bind to negatively charged membranes and subsequently lyse them . The outer membrane of cancer cells contain negatively charged phosphatidylserine, which may contribute to the anticancer properties of AMPs . However, the utilization of native AMPs is limited, as their function is compromised in serum because of enzymatic degradation and binding to serum components .…”