Studio di peptidi antimicrobici dell'immunità innata: Possibili applicazioni in campo medico ed agro-alimentare
Ripa, Raffaella (2010) Studio di peptidi antimicrobici dell'immunità innata: Possibili applicazioni in campo medico ed agro-alimentare. [Tesi di dottorato] (Inedito)
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The antimicrobial peptides are a large and diversified group of effector molecules of the innate immune response and constitute the first line of defense against the pathogens. The AMPs (antimicrobial peptides) are produced by several tissues and cell types in plants and in animal species like insects,amphibians and vertebrate. Their aminoacid composition and their chimical-phisical caracteristics linked with structural characteristics, allow them to act with the lipid bilayer of the bacterial membrane, causing the death of microorganisms. The antimicrobial agents seem to have an high potential action on bacterial pathogens for humans, because they are able to act in a selective and combined manner. Moreover they do not induce the phenomenon of antibiotic-resistant on bacteria, which is a quite common factor in traditional antibiotics. One of the richest natural sources of peptide antibiotics are the secretions of the amphibians and the molecules produced by insects to the defense from external insults. Therefore, it was decided to analyze some of these molecules, which have small size, strong α-helix structure, and positive net charge, such as Temporins, from the skin of the European red frog (Rana temporaria). The second type of analyzed molecules are Royal-Jelline, produced by cephalic glands of nurse bees (Apis mellifera). The research activities, carried out during the PhD, is part of the DEFENCE project. Studies about the action mechanism of these molecules against opportunistic pathogens, involved in nosocomial infections or associated with food poisoning, have shown their ability to alter the membrane permeability of the target cell, and to act synergistically. In particular, we used a synthetic analogue of Temporin B (TB-KK), which becames able to act in synergy with Temporin A and Royal-Jellina 1. In addition, the mix of Temporin A and Temporin B (TB-KK) was analyzed in live on model organisms (mice) to determine their ability to protect the animal against Gram-positive and Gram-negative and to exert an anti- inflammatory activities, modulating the expression of inflammatory cytokines. Purpose of this study is the identification of peptides, which have the best therapeutic index for protection both from bacterial infections and bacterial components (LPS), main agents of the sepsis pathogenesis. A further aim is finding a possible application of these peptides is in farmacology end agro-industries, as an active-packaging component to increase shelf-life of alimentary products.
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