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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Amino Acid Sequence, Animals, Anti-Bacterial Agents, Anticoagulants, Bacteria, Blood Coagulation, Cytokines, Disease Models, Animal, Escherichia coli, Female, Glycoproteins, Gram-Negative Bacteria, Gram-Negative Bacterial Infections, Hemolysis, Humans, Hydrophobic and Hydrophilic Interactions, Male, Mice, Mice, Inbred BALB C, Microbial Viability, Peptides, Phylogeny, Plasma, Pseudomonas aeruginosa, Sepsis, Sequence Alignment, Sequence Homology, Species Specificity, Vertebrates.
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Do vertebrate TFPI-2 C-terminal peptides exert therapeutic applications against Gram-negative infections? Context: Tissue factor pathway inhibitor-2 (TFPI-2) is a serine protease inhibitor that exerts multiple physiological and patho-physiological activities involving the modulation of coagulation, angiogenesis, tumor invasion, and apoptosis. In previous studies we reported a novel role of human TFPI-2 in innate immunity by serving as a precursor for host defense peptides. Here we employed a number of TFPI-2 derived peptides from different vertebrate species and found that their antibacterial activity is evolutionary conserved although the amino acid sequence is not well conserved. We further studied the theraputic potential of one selected TFPI-2 derived peptide (mouse) in a murine sepsis model. Hydrophobicity and net charge of many peptides play a important role in their host defence to invading bacterial pathogens. In vertebrates, the C-terminal portion of TFPI-2 consists of a highly conserved cluster of positively charged amino acids which may point to an antimicrobial activity. Thus a number of selected C-terminal TFPI-2 derived peptides from different species were synthesized and it was found that all of them exert antimicrobial activity against E. coli and P. aeruginosa. The peptide-mediated killing of E. coli was enhanced in human plasma, suggesting an involvement of the classical pathway of the complement. Under in vitro conditions the peptides displayed anti-coagulant activity by modulating the intrinsic pathway of coagulation and in vivo treatment with the mouse derived VKG24 peptide protects mice from an otherwise lethal LPS shock model.
assistant
Our results suggest that the evolutionary conserved C-terminal part of TFPI-2 is an interesting agent for the development of novel antimicrobial therapies. Final Decision: yes