title: Functional characterization of codCath, the mature cathelicidin antimicrobial peptide from Atlantic cod (Gadus morhua).
abstract: Cathelicidins are among the best characterized antimicrobial peptides and have been shown to have an important role in mammalian innate immunity. We recently isolated a novel mature cathelicidin peptide (codCath) from Atlantic cod and in the present study we functionally characterized codCath. The peptide demonstrated salt sensitivity with abrogation of activity at physiological salt concentrations. In low ionic strength medium we found activity against marine and non-marine Gram-negative bacteria with an average MIC of 10 μM, weak activity against a Gram-positive bacterium (MIC 80 μM), and pronounced antifungal activity (MIC 2.5 μM). The results suggest the kinetics and mode of action of codCath to be fast killing accompanied by pronounced cell lysis. Extracellular products (ECPs) of three marine bacteria caused breakdown of the peptide into smaller fragments and the cleaved peptide lost its antibacterial activity. Proteolysis of the peptide on the other hand was abolished by prior heat-treatment of the ECPs, suggesting a protease involvement. We observed no cytotoxicity of the peptide in fish cells up to a concentration of 40 μM and the selectivity of activity was confirmed with bacterial and mammalian membrane mimetics. We conclude that the potent broad-spectrum activity of codCath hints at a role of the peptide in cod immune defense.
authors.affiliation: Institute of Biology, University of Iceland, Reykjavik, Iceland. dcb1@hi.is
authors.forename: Daniela C
authors.initials: DC
authors.lastname: Broekman
authors.forename: Alexandra
authors.initials: A
authors.lastname: Zenz
authors.forename: Bjarnheidur K
authors.initials: BK
authors.lastname: Gudmundsdottir
authors.forename: Karl
authors.initials: K
authors.lastname: Lohner
authors.forename: Valerie H
authors.initials: VH
authors.lastname: Maier
authors.forename: Gudmundur H
authors.initials: GH
authors.lastname: Gudmundsson
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism*; D023181:Antimicrobial Cationic Peptides; D001419:Bacteria / Q000187:drug effects / Q000201:enzymology; D054804:Cathelicidins / Q000235:genetics / Q000378:metabolism*; D005658:Fungi / Q000187:drug effects; D048389:Gadus morhua / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D008826:Microbial Sensitivity Tests; D059748:Proteolysis; D012492:Salts / Q000737:chemistry; D012623:Seawater
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D012492:Salts