Membrane-active peptide PV3 efficiently eradicates multidrug-resistant Pseudomonas aeruginosa in a mouse model of
Hamed Memariani1, Delavar Shahbazzadeh1, Jean-Marc Sabatier2
1Venom and Biotherapeutics Molecules Lab., Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
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.
Insights
Peptide PV3 demonstrates potent topical bactericidal activity against multidrug-resistant Pseudomonas aeruginosa. This novel antimicrobial agent effectively eradicates bacteria in a mouse burn model with no observed skin toxicity.
Area of Science:
- Antimicrobial Peptides
- Bacteriology
- Wound Infection Models
Background:
- Multidrug-resistant (MDR) Pseudomonas aeruginosa poses a significant threat in clinical settings.
- Development of novel antimicrobial agents is crucial to combat antibiotic resistance.
Purpose of the Study:
- To evaluate the topical bactericidal efficacy of peptide PV3 against MDR Pseudomonas aeruginosa.
- To assess the safety and killing kinetics of PV3 in a mouse burn infection model.
Main Methods:
- Structural analysis of PV3 using circular dichroism spectroscopy.
- Confocal microscopy to determine the mechanism of action.
- In vitro and in vivo efficacy testing in a mouse burn wound model comparing PV3 to doripenem.
- Histopathological analysis of mouse skin for toxicity assessment.
Main Results:
- Peptide PV3 showed high helical content in a hydrophobic buffer, indicating structural adaptability.
- PV3 demonstrated superior in vitro activity and faster killing kinetics than doripenem.
- A single topical dose of PV3 eradicated MDR P. aeruginosa in a mouse burn model, while doripenem failed.
- Histopathology confirmed no topical skin toxicity associated with PV3 treatment.
Conclusions:
- Peptide PV3 exhibits potent, rapid, and safe topical bactericidal activity against MDR P. aeruginosa.
- PV3 is a promising candidate antimicrobial agent for treating infections caused by antibiotic-resistant bacteria.
- The findings support further investigation of PV3 as a therapeutic option for resistant bacterial infections.
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