Antimicrobial activity of rabbit CAP18-derived peptides.
A cationic antimicrobial protein of 18 kDa (CAP18) was originally isolated from rabbit granulocytes by using as an assay the agglutination of Re-lipopolysaccharide-coated erythrocytes. The C-terminal 37 amino acids of CAP18 (CAP18(106-142)) make up the lipopolysaccharide-binding domain. Synthetic CAP18(106-142) has broad antimicrobial activity against both gram-positive (50% inhibitory concentration, 130 to 200 nM) and gram-negative (50% inhibitory concentration, 20 to 100 nM) bacteria. Susceptible strains include Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhimurium. Antimicrobial activity is highly dependent on peptide structure. Although a 32-amino-acid peptide resulting from the truncation of 5 amino acids from the C terminus of CAP18(106-142) is highly active, other fragments of CAP18(106-142), including CAP18(106-142) with a truncated N terminus, do not exhibit antimicrobial activity. Unlike previously characterized antimicrobial peptides derived from granulocyte proteins, CAP18(106-142) is active in serum. CAP18(106-142) or a derivative peptide may have therapeutic potential for bacterial sepsis.
Larrick
J W
JW
Palo Alto Institute of Molecular Medicine, Mountain View, California 94043.
Hirata
M
M
Shimomoura
Y
Y
Yoshida
M
M
Zheng
H
H
Zhong
J
J
Wright
S C
SC
D000372:Agglutination Tests; D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins / Q000494:pharmacology*; D054804:Cathelicidins; D004912:Erythrocytes / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D012756:Sheep; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins; D054804:Cathelicidins; D008070:Lipopolysaccharides; D010446:Peptide Fragments