Anti-microbial 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.


OBJECTIVE
To evaluate the antimicrobial activity of C-terminal peptides derived from human CAP18.


METHODS
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 micrograms/ml) and gram-negative bacteria (IC50 = 0.5-5 micrograms/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.


CONCLUSIONS
Human CAP18(104-140) or a derivative peptide may have therapeutic potential for bacterial sepsis.
Larrick
J W
JW
Palo Alto Institute of Molecular Medicine, Mountain View, CA 94043, USA.
Hirata
M
M
Zhong
J
J
Wright
S C
SC
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins / Q000494:pharmacology*; D054804:Cathelicidins; D003001:Cloning, Molecular; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals / Q000737:chemistry; D017433:Protein Structure, Secondary; D011817:Rabbits
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins; D054804:Cathelicidins; D008070:Lipopolysaccharides; D021382:Protein Sorting Signals