TO17: A teleost antimicrobial peptide that induces degradation of bacterial nucleic acids and inhibits bacterial infection in red drum, Sciaenops ocellatus

Tissue factor pathway inhibitor (TFPI)-1 is well known for its role as an inhibitor of blood coagulation. Several studies have demonstrated that the C-terminal peptides of TFPI-1 are active against a broad spectrum of microorganisms. In a previous study, we found that TO17 (with 17 amino acids), a TFPI-1 C-terminal peptide from red drum (Sciaenops ocellatus), was active against Edwardsiella tarda. In the present study, we investigated further the antimicrobial spectrum, action mode, as well as the immunostimulatory property of TO17. Our results showed that TO17 displayed antimicrobial activity against Staphylococcus aureus, Micrococcus luteus, Vibrio vulnificus, and infectious spleen and kidney necrosis virus, independent of host serum. Furthermore, the activity of TO17 was influenced by the length or type of amino acids at the N and C termini. During its interaction with V. vulnificus, TO17 exerted its antibacterial activity by destroying cell membrane integrity, penetrating the cytoplasm and inducing degradation of genomic DNA and total RNA. In addition, TO17 had no hemolytic activity against red drum blood cells. In vitro, TO17 enhanced production of nitric oxide and bactericidal activity of red drum macrophages. In vivo, administration of red drum with TO17 before bacterial infection significantly reduced pathogen dissemination and replication in tissues. These results indicate that TO17 is a broad-spectrum antimicrobial peptide with immunostimulatory properties and it has the potential to be used as an antimicrobial agent in aquaculture.