PaP1, a Broad-Spectrum Lysin-Derived Cationic Peptide to Treat Polymicrobial Skin Infections

Area of Science:

• Antimicrobial Peptides
• Bacteriophage Lysins
• Infectious Diseases
• Drug Discovery

Background:

• Polymicrobial skin infections, often complicated by antibiotic resistance, pose significant clinical challenges.
• Bacteriophage lysins and their derived membrane-acting cationic peptides offer potential alternative therapeutics.
• These peptides can permeabilize bacterial membranes, leading to cell death.

Purpose of the Study:

• To evaluate the antibacterial properties of a modified cationic peptide, PaP1, derived from the PlyPa01 lysin.
• To assess PaP1's efficacy against high-priority antibiotic-resistant pathogens, including ESKAPE organisms.
• To investigate PaP1's potential as a monotherapy or adjunctive therapy for topical infections.

Main Methods:

• In vitro bactericidal assays against planktonic and biofilm bacteria.
• Time-kill assays to determine killing kinetics.
• In vivo efficacy studies in a murine burn wound infection model.
• Cytotoxicity assays on human cells.

Main Results:

• PaP1 demonstrated potent in vitro bactericidal activity against Gram-positive and Gram-negative pathogens, including ESKAPE strains.
• The peptide was effective against both planktonic and biofilm bacteria, killing on contact and stable across various pH and temperature ranges.
• In vivo studies showed PaP1 enhanced topical antibiotic efficacy in treating infected burn wounds, with no observed cytotoxicity to human cells.

Conclusions:

• PaP1 is a potent, broad-spectrum antimicrobial peptide with significant potential for topical applications.
• Its ability to overcome antibiotic resistance and enhance existing therapies makes it a promising candidate for treating polymicrobial infections.
• Further preclinical development is warranted to establish PaP1 as a viable therapeutic agent.