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Titre : | Régulation dun nouveau mécanisme de compétition des Bacteroidetes : Protéines Antimicrobiennes Sécrétées par les Bacteroidetes (BSAPs) |
Auteurs : | Chloé Petre, Auteur ; Frédéric Lauber, Promoteur |
Type de document : | Travail de fin d'études |
Editeur : | Woluwe-Saint-Lambert : Haute École Léonard de Vinci, 2024 |
Index. décimale : | TFE - Biologie médicale |
Mots-clés: | Bacteroidetes ; Protéines de surface ; Interactions microbiennes ; Comportement compétitif ; Microbiome gastro-intestinal |
Résumé : | This study focuses on Bacteroidales, a family of dominant Gram-negative bacteria in the human intestinal microbiota. These bacteria, essential for human health, secrete specific antimicrobial proteins (BSAPs) that regulate intraspecies competition. Complex bacterial interactions with their environment regulate the long-term colonization of the most adapted strains of Bacteroidales, in turn affecting the overall composition of the human intestinal flora. Specific competition mechanisms are of paramount importance in the dynamics of this ecosystem, allowing a bacterium to directly oppose a competitor to defend its ecological niche. The study aims to understand the regulation of BSAPs expression, an area that is still relatively unexplored but promising for the development of new therapeutic strategies against resistant bacterial infections. By targeting bacterial surface components specifically, BSAPs could effectively modulate the composition of the intestinal microbiota, thereby promoting a healthy microbial flora. We studied the expression of BSAPs by replacing their genes with a reporter gene, NanoLuc, in different strains of Bacteroidales, and subjecting these strains to various experimental conditions. The results, analyzed by bioluminescence and Western Blot, could pave the way for innovative biomedical applications by developing targeted therapies. We focused on the expression BSAP-1 and BSAP-4 in Bacteroides fragilis 638R and analyzed how various environmental factors, such as nutrient availability, the presence of stressors or competitors, influence the expression of these proteins. Overall, the findings confirm that BSAP-4 is expressed at higher levels than BSAP-1, with an opposite expression profile observed between these two lipoproteins. Subcellular fractionation showed that these proteins are mainly localized within the cells rather than in outer membrane vesicles. Other strains of Bacteroidales, such as B. thetaiotaomicron and B. dorei, were also tested, providing interesting preliminary results that need to be further explored. Overall, BSAP-4 is the most expressed protein among those studied. Finally, studying this competition mechanism highlights the crucial role of Bacteroidales Secreted Antimicrobial Proteins in maintaining a microbial balance favorable to health. Further research conducted in this project will allow to fully harness the potential of BSAPs. We hope that one day, traditional antibiotic therapies can be replaced by using these proteins to target pathogens without disrupting the commensal microbiome. |
Disponible en ligne : | Oui |
Lieu du stage : | Institut de Duve Secteur de Biochimie et Recherche métabolique |
Département du TFE : | Biologie médicale |
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