Peptide analogs based on the innate immune system molecule, CAP37, are potent antimicrobials against Pseudomonas aeruginosa and attenuate Pseudomonas LPS‐mediated effects in vitro

Abstract

CAP37 is a neutrophil‐derived protein with strong antimicrobial activity against Gram negative bacteria. The principal antimicrobial domain of CAP37 resides between amino acids 20 and 44. A synthetic peptide based on amino acids 20‐44 (CAP37/20‐44) mimics the antibacterial activity of the native protein. Recently, two further analogs of CAP37/20‐44 were synthesized in which the cysteine residues at positions 26 and 42 were replaced with serine residues. The objective of this study was 1) to evaluate all three CAP37 peptides for their antimicrobial activity against Pseudomonas aeruginosa including clinical isolates with known antimicrobial resistance profiles to conventional antibiotics and 2) to determine their ability to bind and neutralize Pseudomonas lipopolysaccharide (LPS) or endotoxin. The Limulus Amebocyte Lysate assay was used to determine LPS binding. LPS neutralization was determined by measuring the ability of the peptides to attenuate the release of cytokines such as tumor necrosis factor‐alpha from the murine macrophage cell line, RAW264.7. Our findings demonstrate that all three synthetic peptides showed bactericidal activity against Pseudomonas including the clinical isolates and that they bound and neutralized the toxic effects of LPS in vitro. We conclude that synthetic CAP37 peptides have strong potential as therapeutics against Pseudomonas infections. Support: NIH UO1AI075391.