Design, synthèse et étude-structure activité des bactériocines synthétiques pour l'utilisation dans les secteurs alimentaire, vétérinaire et médical

Authors: Bédard, François
Advisor: Biron, ÉricFliss, Ismaïl
Abstract: Antibiotic resistance has become a major problem in the prevention and treatment of bacterial infections. As they demonstrate in vitro inhibitory activities against a large number of clinically important pathogenic bacteria, bacteriocins are increasingly seen as a potential alternative to conventional antibiotics. Despite this enormous potential, their use is greatly limited by the high costs associated with their production by fermentation. The chemical synthesis of the latter has been considered, but no approach has yielded so far a yield that can significantly reduce production costs. In order to develop an efficient synthetic route for these antibacterial peptides, we used as model the pediocin PA-1, a class IIa bacteriocin with anti-Listeria activity. Optimization of the synthetic approach allowed us to increase yields by 1% to 45% and to design analogues with improved pharmacological properties such as greater resistance to oxidation and enzymatic lysis. This important achievement allowed us to not only produce bacteriocin in large quantities but also to determine its three-dimensional structure and to evaluate its impact on the microbiota in the human gastrointestinal tract. The approach developed has also been shown to be effective for the production of other class II bacteriocins such as Bactofencin A and allows targeting more pathogens found in the different food, veterinary and medical sectors. In addition to describing the synthesis and structure-activity studies of Bactofencin A, this book presents the strategies used to produce and determine the structure of pediocin PA-1 as well as studies on its antimicrobial activity and its effects on microbiota. the gastrointestinal tract.
Document Type: Thèse de doctorat
Issue Date: 2018
Open Access Date: 29 January 2019
Grantor: Université Laval
Collection:Thèses et mémoires

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