EDTA enhances antimicrobial activity of PR-39 and Protegrin-1 antimicrobial peptides against carbapenem-resistant Pseudomonas aeruginosa in serum

Carbapenem-resistant Pseudomonas aeruginosa represents a frequent and clinically challenging pathogen responsible for both acute and chronic infections. Antimicrobial peptides are emerging as a promising class of novel therapeutic agents due to their broad-spectrum activity, rapid bactericidal activity, and low potential to induce antimicrobial resistance. The antimicrobial efficacy of these peptides can be further enhanced by EDTA. However, their activity is often reduced in the presence of serum, which contains multiple inhibitory components. In this study, EDTA fully restored the antimicrobial activity of PR-39 and Protegrin-1 in serum. Moreover, incorporation of chitosan increased the antimicrobial efficacy of the PR-39/Protegrin-1/EDTA formulation. These findings demonstrate that PR-39, Protegrin-1, EDTA, and chitosan can act synergistically, supporting the feasibility of integrating these components into a unified therapeutic platform.