ANTIMICROBIAL ACTIVITY OF HUMAN CAP18 PEPTIDES

Background: CAP18 derived from rabbit leukocytes is a 142-amino acid protein recently demonstrated to have Lipopolysaccharide (LPS) binding and anti-microbial activity. The C-terminal 37 amino acids of rabbit CAP18 (CAP18(106-142)) comprise the LPS-binding and anti-microbial domain. The homologous domain of human CAP18 (huCAP18(104-140)) was identified from the recently cloned human CAP18 cDNA. Objectives: To evaluate the antimicrobial activity of C-terminal peptides derived from human CAP18. Study design: Prepare synthetic human CAP18(104-140) and study anti-microbial activity versus various gram-negative and gram-positive bacteria. Results: Synthetic human CAP18(104-140) has broad anti-microbial activity versus both gram-positive (IC50 = 2.5 mu g/ml) and gramnegative bacteria (IC50 = 0.5-5 mu g/ml). Susceptible strains include Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhimurium. A 32-amino acid peptide lacking five amino acids from the C-terminus of CAP18(104-140) has higher activity. Unlike previously characterized anti-microbial peptides derived from granulocyte proteins, CAP18(104-140) is active in serum. Conclusion: Human CAP18(104-140) or a derivative peptide may have therapeutic potential for bacterial sepsis.