Peptide antibiotics from mast cells of fish

Antimicrobial peptides are increasingly recognized as a critical first line of host defense mechanism against pathogenic bacteria, fungi, parasites and viruses. They have been isolated from myeloid cells and mucosal tissues of many vertebrates, as well as from procaryotes, plants and invertebrates. Here we show the isolation of a novel family of peptide antibiotics, which we have named “piscidins” (from “Pisces” meaning fish), from an important aquaculture fish, hybrid striped bass (Morone saxatilis x M. chrysops). These peptides were purified through multiple electrophoretic and chromatographic methods to obtain putative peptides by reverse-phase HPLC. Mass spectrometry and amino acid sequence analysis indicated that they are 22 amino acids in length. Piscidins have no known sequence homology with any reported sequences in the NIH blast database and thus constitute a new family of peptide antibiotics. Schiffer-Edmundson plots predicted that piscidins adopt an amphipathic α-helical conformation, which is typical of most linear antimicrobial peptides. Piscidins have potent, broad-spectrum antibacterial activity, which is often below the lowest detectable hemolytic concentration. Important bacterial pathogens of both fish and mammals, including multidrug-resistant pathogens are very susceptible to piscidins. Immunohistochemistry located piscidins in many tissues, including skin, gill, and gastrointestinal tract. Piscidins reside in mast cells, a highly common tissue granulocyte of uncertain function, which is ubiquitous in fish and other vertebrates. The mast cells of other members of the Suborder Percoidei are immunohistochemically positive for piscidins, suggesting that piscidins may be an evolutionarily conserved defense in this very important group. Since peptide antibiotics occur in mast cells of fish, we speculate that this innate defense might also occur in mast cells of other vertebrates. This finding also suggests that mast cells may play a critical role in innate host defense by utilizing these peptide antibiotics. No peptide antibiotic has previously been isolated from mast cells of any animal, including mammals.