| Cationic antimicrobial peptides are components of the host innate immune response against infections in almost all species. Although innate defenses in fish are particularly important due to a frequently late onset and short duration of the secondary immune response in these animals, few fish peptides have been studied to date.; This research identifies a novel H1-histone derived cationic peptide (HSDF-1) from coho salmon (Oncorhynchus kisutch), and describes the design, as well as the antibacterial, membrane, and intracellular activities of several other fish-based synthetic peptides of potential importance in aquaculture.; HSDF-1, a 26 residue species identical to the N-terminal segment of trout H1 histone, was isolated from the serum and mucus of disease-challenged coho salmon. The purified fractions inhibited the growth of antibiotic-supersusceptible S. typhimurium, as well as A. salmonicida and V. anguillarum. Synthetic HSDF-1 and its derivative HSDF-2 were inactive in antimicrobial assays, but they potentiated the antimicrobial activities of the flounder peptide pleurocidin, lysozyme, and crude lysozyme-containing extracts from coho salmon. Although the peptides inserted specifically into anionic lipid monolayers, synergy with pleurocidin did not appear to occur at the cytoplasmic membrane level.; The effects of pleurocidin and several of its derivatives on bacterial membranes and intracellular functions were further studied to gain insight into the mode of action of these fish-derived peptides. All peptides tested at their minimal inhibitory concentrations (MICs) inhibited macromolecular synthesis in bacteria, causing a decrease in the incorporation of [3H]thymidine, [3H]uridine, or [3H]histidine into DNA, RNA, and proteins, respectively. However, many of the peptides applied at their MICs showed limited or negligible ability to damage bacterial cytoplasmic membranes, as observed using a fluorescent dye (diSC35) assay. The inhibition of macromolecular synthesis may thus be a result of the peptides entering bacterial cells and acting intracellularly in a direct fashion, as suggested by the fact that when two peptides were tested, they were able to translocate into liposomes without lysing them.; A combined approach of isolating antimicrobial peptides from nature and designing them from existing templates, should eventually provide the medical and veterinary clinicians with a useful arsenal of weapons in the face of developing resistance to conventional antibiotics. |
