Antibacterial, Antibiofilm, and Anti-inflammatory Effects of a Novel Thrombin-Derived Peptide in Sepsis Models: Insights into Underlying Mechanisms

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