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Virulence Des Escherichia Coli Entérohémmoragiques: Rôle Central

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Virulence Des Escherichia Coli Entérohémmoragiques: Rôle Central Virulence des Escherichia coli entérohémmoragiques : rôle central du monoxyde d’azote dans le devenir de l’infection et identification de nouveaux déterminants impliqués dans l’adaptation du pathogène à l’envirronement digestif Marion Gardette To cite this version: Marion Gardette. Virulence des Escherichia coli entérohémmoragiques : rôle central du monoxyde d’azote dans le devenir de l’infection et identification de nouveaux déterminants impliqués dans l’adaptation du pathogène à l’envirronement digestif. Bactériologie. Université Clermont Auvergne, 2019. Français. NNT : 2019CLFAC075. tel-02954350 HAL Id: tel-02954350 https://tel.archives-ouvertes.fr/tel-02954350 Submitted on 1 Oct 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITÉ CLERMONT-AUVERGNE CLERMONT-FERRAND ÉCOLE DOCTORALE DES SCIENCES DE LA VIE, SANTÉ, AGRONOMIE, ENVIRONNEMENT N° d’ordre : Thèse Présentée à l’Université Clermont-Auvergne pour l’obtention du grade de DOCTEUR D’UNIVERSITÉ Spécialité Génétique, Physiologie, Pathologie, Nutrition, Microbiologie Santé et Innovation Soutenue le 02 Décembre 2019 MARION GARDETTE Virulence des Escherichia coli entérohémorragiques : rôle central du monoxyde d'azote dans le devenir de l'infection et identification de nouveaux déterminants impliqués dans l'adaptation du pathogène à l'environnement digestif Rapporteurs Josée Harel, PR, GREMIP, Saint-Hyacinthe, Canada Suzana Salcedo, CR, UMR5086 MMSB, Lyon, France Examinateurs Stéphane Bonacorsi, PR, Service de Microbiologie Hôpital Robert-Debré, Paris, France Nicolas Barnich, PR, UMR1071 M2iSH, Clermont-Ferrand, France Directeur de Grégory Jubelin, CR, UMR454 MEDiS, Clermont-Ferrand, France thèse Encadrante Estelle Loukiadis, ISPV, UMR5557 Écologie Microbienne, Marcy-l'Étoile, de thèse France Unité Microbiologie Environnement Digestif et Santé, UMR454, UCA, INRA Clermont Ferrand/Theix UNIVERSITÉ CLERMONT-AUVERGNE CLERMONT-FERRAND ÉCOLE DOCTORALE DES SCIENCES DE LA VIE, SANTÉ, AGRONOMIE, ENVIRONNEMENT N° d’ordre : Thèse Présentée à l’Université Clermont-Auvergne pour l’obtention du grade de DOCTEUR D’UNIVERSITÉ Spécialité Génétique, Physiologie, Pathologie, Nutrition, Microbiologie Santé et Innovation Soutenue le 02 Décembre 2019 MARION GARDETTE Virulence des Escherichia coli entérohémorragiques : rôle central du monoxyde d'azote dans le devenir de l'infection et identification de nouveaux déterminants impliqués dans l'adaptation du pathogène à l'environnement digestif Rapporteurs Josée Harel, PR, GREMIP, Saint-Hyacinthe, Canada Suzana Salcedo, CR, UMR5086 MMSB, Lyon, France Examinateurs Stéphane Bonacorsi, PR, Service de Microbiologie Hôpital Robert-Debré, Paris, France Nicolas Barnich, PR, UMR1071 M2iSH, Clermont-Ferrand, France Directeur de Grégory Jubelin, CR, UMR454 MEDiS, Clermont-Ferrand, France thèse Encadrante Estelle Loukiadis, ISPV, UMR5557 Écologie Microbienne, Marcy-l'Étoile, de thèse France Unité Microbiologie Environnement Digestif et Santé, UMR454, UCA, INRA Clermont Ferrand/Theix REMERCIEMENTS Cette thèse a débuté dans l’Unité de Microbiologie de l’INRA de Theix dirigée par Régine Talon que je remercie de m’avoir accueillie au sein de son laboratoire. L’Unité est ensuite devenue UMR MEDiS sous la direction de Pierre Peyret et d’Annick Bernalier-Donadille, que je remercie également. J’ai également passé 7 mois dans l’équipe Bactéries Pathogènes Opportunistes et Environnement (BPOE) de l’UMR Ecologie Microbienne, dirigée par Benoit Cournoyer, que je remercie pour son accueil. Tous mes remerciements vont à mon directeur de thèse Grégory Jubelin, pour son encadrement et la confiance qu'il m'a accordée durant ce travail. Merci pour ta disponibilité au cours de ces 3 années, de m’avoir toujours guidée et soutenue pour mener à bien ce projet. Merci pour tous tes conseils scientifiques et techniques, et pour m’avoir apporté ton soutien autant lors des manips que lors de la rédaction de ce manuscrit. Merci ensuite à Estelle Loukiadis, ma co-directrice, pour avoir encadré ma thèse et m’avoir fait confiance tout au long de ce projet. Merci également pour tes précieux conseils scientifiques. Je tiens également à remercier les membres de mon jury de thèse, Josée Harel et Suzana Salcedo pour m’avoir fait l’honneur d’accepter d’être rapporteurs de ce travail ; Stéphane Bonacorsi et Nicolas Barnich pour leur participation en tant qu’examinateurs. Je remercie Hang Nguyen et Stéphane Junot pour avoir fait partie de mes comités de suivi de thèse. Merci pour vos conseils scientifiques qui m’ont permis d’avancer. Je tiens également à remercier tous les membres de l’équipe MEDiS. En particulier, merci Annie, pour ton aide technique et pour ta sympathie. Merci Valérie pour m’avoir accompagnée et rassurée lors des premières manips avec les souris. Katy, merci pour ta bonne humeur quotidienne et ton rire qui résonne toujours dans les couloirs du labo. Merci également à Gloglo pour ta gentillesse. Merci à mes colocs de bureau, Ruben et Phiphi, pour m’avoir toujours poussée à travailler plus (et à réduire le temps perdu sur les réseaux sociaux…), en particulier pendant la rédaction, merci pour votre bonne humeur et votre humour. Merci aux stagiaires de l’équipe, Sarah et Ines, pour votre soutien. Sarah, j’espère que tu trouveras vite ta voie, et Ines, je compte sur toi pour reprendre dignement le flambeau de la thésarde de l’équipe, profite bien de ces 3 années. Merci enfin à Floflo, Yacine, Chloé et Julien, merci pour tous ces moments passés au labo et en dehors, pour toutes ces discussions et débats inutiles, pour votre humour et votre soutien moral tout au long de ces 3 ans. Un merci particulier à Julien, pour ton aide (plus ou moins efficace) dans toutes les manips, et surtout parce que je ne serai pas en train d’écrire cette thèse si tu n’avais pas été là, alors merci mamène ! Je remercie également toute l’équipe BPOE pour leur accueil pendant ces quelques mois. Merci à tous pour votre gentillesse. En particulier merci à la team du RU, Thomas, Marion et Sarah, je garde un très bon souvenir de nos conversations sérieuses et moins sérieuses. Merci Thomas, de m’avoir fait une place dans ton bureau, et pour tous tes précieux conseils scientifiques et autres. Merci aussi à Delphine, pour ta gentillesse et ta disponibilité. Merci à Thierry Marchal, du laboratoire d’Histologie de Vetagro Sup et à toute son équipe pour leur accueil, leur gentillesse, et le temps qu’ils m’ont accordé pour m’initier à l’Histologie. A titre plus personnel, je souhaiterais d’abord remercier Cécile, pour avoir été là pendant ces 3 ans, pour m’avoir hébergée quand j’étais à la rue, et pour avoir toujours été fidèle au poste pour nos rendez-vous hebdomadaires, merci vieille meuf ! Merci ensuite à mes amis du Beaujolais, difficile de tous vous citer mais les week-ends passés au vert avec vous ont toujours été salvateurs. Un merci tout particulier à vous, Manon et Margaux. Votre soutien au quotidien m’a sans aucun doute permis d’arriver au bout de cette thèse, merci d’avoir toujours été là pour me remonter le moral malgré la distance. Ensuite, comment ne pas citer ces inconnus, qui en l’espace de quelques semaines sont devenus une seconde famille. Les colocs du Petit Château d’abord, Johan, JB, Vincent, Charlyne, Yasmine et Thibaud, vous avez embelli mes soirées lyonnaises et vous avez réussi à me redonner le sourire dans une période compliquée. Mes colocs clermontois ensuite… Amélie, Antho, Bibiche, Matth, Mavava, Mimo et Paupau, cette dernière année a sans aucun doute été la meilleure et c’est entièrement grâce à vous. Merci pour tous ces moments partagés, j’emporte avec moi un tas de souvenirs inoubliables. Enfin, merci à ma famille, celle qui est à mes côtés depuis 25 ans cette fois-ci. Merci à mes parents et mes frères qui m’ont soutenue dans tous les projets qui m’ont menée ici aujourd’hui, et qui ont toujours été présents pendant ces 3 années. Et pour finir, une pensée pour ma petite mamie. Tu étais là quand j’ai commencé cette aventure, j’aurai aimé que tu sois présente pour me voir franchir la ligne d’arrivée, tu me manques. Table des matières Sommaire Liste des Tableaux ................................................................................................................ 5 Liste des Figures ................................................................................................................... 6 Liste des Abréviations........................................................................................................... 7 CONTEXTE DU PROJET .............................................................................................................. 10 REVUE DE LITTERATURE ............................................................................................................ 14 Partie I : Le Monoxyde d’Azote - NO .................................................................................. 15 I. Propriétés biochimiques du NO ............................................................................. 15 1. Réactions avec l’oxygène et ses dérivés ...........................................................
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