Antibacterial,\nAntibiofilm, and Anti-inflammatory\nEffects of a Novel Thrombin-Derived Peptide in Sepsis Models: Insights\ninto Underlying Mechanisms

We developed two short helical antimicrobial peptides,\nHVF18-a3\nand its d-enantiomer, HVF18-a3-d, derived from the thrombin\nC-terminal peptide HVF18. These peptides exhibit potent antimicrobial\nactivity against various bacteria by compromising both the outer and\ninner membranes, with low hemolytic activity. They are stable in the\npresence of physiological salts and human serum, exhibiting a low\npotential for developing drug resistance and excellent antibiofilm\nactivity against Gram-negative bacteria. HVF18-a3-d also neutralized\nlipopolysaccharide (LPS) through direct binding interactions and suppressed\nthe production of inflammatory cytokines through the inflammatory\nsignaling pathway mediated by Toll-like receptor 4 in RAW264.7 cells\nstimulated with LPS. Both pre- and post-treatment with HVF18-a3-d\nsignificantly protected mice against fatal septic shock induced by\ncarbapenem resistant Acinetobacter baumannii. These findings suggest HVF18-a3 and HVF18-a3-d are promising candidates\nfor developing antibiotics against Gram-negative sepsis.