Many chemokines including CCL20/MIP-3alpha display antimicrobial activity.
Previous studies have demonstrated that beta-defensins exhibit chemotactic activity by sharing the chemokine receptor CCR6 with the CC chemokine ligand CCL20/macrophage-inflammatory protein-3alpha (MIP-3alpha). Structural analysis of CCL20/MIP-3alpha revealed that most of the positively charged residues are concentrated at one area of its topological surface, a characteristic considered to be important for the antimicrobial activity of defensins. Here, we report that similar to defensins, CCL20/MIP-3alpha has antimicrobial effects on Escherichia coli, Pseudomonas aeruginosa, Moraxella catarrhalis, Streptococcus pyogenes, Enterococcus faecium, Staphylococcus aureus, and Candida albicans. Additionally, by screening a total of 30 human chemokines, we have identified an additional 17 human chemokines, which exhibit antimicrobial activity in vitro. Collectively, about two-thirds of the chemokines investigated so far has the capacity to kill microorganisms in vitro, suggesting that antimicrobial activity may be another host-defense function for certain chemokines. Comparison of the structural characteristics between antimicrobial and nonantimicrobial chemokines suggests that topological formation of a large, positively charged electrostatic patch on the surface of the molecule is likely to be a common structural feature of antimicrobial chemokines.
Yang
De
D
Division of Cancer Treatment and Diagnosis, Science Applications International Corp., Inc.-Frederick, Maryland 21702, USA.
Chen
Qian
Q
Hoover
David M
DM
Staley
Patricia
P
Tucker
Kenneth D
KD
Lubkowski
Jacek
J
Oppenheim
Joost J
JJ
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D054418:Chemokine CCL20; D018925:Chemokines / Q000494:pharmacology; D019742:Chemokines, CC / Q000494:pharmacology*; D015169:Colony Count, Microbial; D005658:Fungi / Q000187:drug effects*; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D023083:beta-Defensins / Q000737:chemistry* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000935:Antifungal Agents; C108355:CCL20 protein, human; D054418:Chemokine CCL20; D018925:Chemokines; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D011994:Recombinant Proteins; D023083:beta-Defensins