GÈNES ESSENTIELS ET VOIES MÉTABOLIQUES DE PSEUDOMONAS AERUGINOSA OPRD MUTANT À L’ORIGINE DE LA PATHOGÉNICITÉ VIS-À-VIS DE L’ÉPITHÉLIUM DES VOIES RESPIRATOIRES HUMAINES (GOAL)
Etablissement : Université de Reims Champagne – Ardenne
École doctorale : Sciences Fondamentales – Santé
Spécialité : Aspects moléculaires et cellulaires de la biologie
Unité de recherche : P3CELL – Pathologies Pulmonaires et Plasticité Cellulaire
Informations sur le site de l’ADUM : https://www.adum.fr/as/ed/
Début de la thèse : 1 octobre 2020
Date limite de candidature : 26 juin 2020
Description de la problématique de recherche :
La perte de la porine OprD, qui est le canal d’entrée des carbapénèmes, entraîne la résistance de Pseudomonas aeruginosa à cette classe d’antibiotiques. Nous avons montré que la perte d’OprD s’accompagnait d’une virulence accrue de P. aeruginosa vis-à-vis de l’épithélium des voies respiratoires humaines. L’objectif de ce travail est de définir le mécanisme expliquant pourquoi l’absence de la porine OprD s’accompagne d’une augmentation de pathogénicité afin de trouver de nouvelles pistes thérapeutiques. Pour cela, nous utiliserons, d’une part, une approche génomique de type Tn-Seq pour déterminer les gènes essentiels de P. aeruginosa OprD mutant lors de l’infection de l’épithélium des voies respiratoires humaines, et d’autre part, une approche phénomique de type phénotypage à haut-débit pour établir les voies métaboliques en lien avec les génotypes identifiés. Ces techniques seront utilisées sur des modèles ex vivo d’épithéliums des voies aériennes humaine cultivés en interface air-liquide et in vivo de pneumonie aiguë chez la souris.
Mots clés : Pseudomonas aeruginosa, séquençage à haut débit, culture cellulaire, modèle murin, génomique
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