Antibacterial, Antibiofilm, and Anti-inflammatory Effects of a Novel Thrombin-Derived Peptide in Sepsis Models: Insights into Underlying Mechanisms. J Med Chem 2024 Nov 14;67(21):19791-19812
Date
10/30/2024Pubmed ID
39475485DOI
10.1021/acs.jmedchem.4c02157Scopus ID
2-s2.0-85208025823 (requires institutional sign-in at Scopus site) 13 CitationsAbstract
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.
Author List
Kumar SD, Lee JK, Radhakrishnan NK, Bang JK, Kim B, Chaudhary SC, Chelladurai A, Ganbaatar B, Kim EY, Lee CW, Yang S, Kim Y, Shin SYAuthor
Ajish Chelladurai Postdoctoral Researcher 3 in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Acinetobacter baumanniiAnimals
Anti-Bacterial Agents
Anti-Inflammatory Agents
Biofilms
Gram-Negative Bacteria
Humans
Lipopolysaccharides
Mice
Microbial Sensitivity Tests
RAW 264.7 Cells
Sepsis
Thrombin
