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These De Doctorat De 2018 - 14 THESE DE DOCTORAT DE AGROCAMPUS OUEST COMUE UNIVERSITE BRETAGNE LOIRE ECOLE DOCTORALE N° 600 Ecole doctorale Ecologie, Géosciences, Agronomie et Alimentation Spécialité : Biochimie, biologie moléculaire et cellulaire Par Fillipe Luiz ROSA DO CARMO La protéine de couche de surface SlpB assure la médiation de l’immunomodulation et de l’adhésion chez le probiotique Propionibacterium freudenreichii CIRM-BIA 129 Thèse présentée et soutenue à AGROCAMPUS OUEST campus de Rennes, le 6 septembre 2018 Unité de recherche : UMR INRA AGROCAMPUS OUEST Science et Technologie du lait et de l’œuf (STLO) Thèse en Cotutelle : Université Fédérale du Minas Gerais Thèse N° : 2018-14 _ B-315 Rapporteurs avant soutenance : Aristóteles Góes Neto Professeur Université fédérale du Minas Gerais, Brésil. Muriel Thomas Directrice de recherche INRA UMR1319 Micalis, Jouy en Josas. Composition du Jury : Président : Françoise Nau Professeur AGROCAMPUS OUEST-Rennes Examinateurs : Nathalie Desmasures Professeur Université de Caen Normandie, Caen Benoit Foligné Université du Droit et de la Santé Lille 2, Lille Dir. de thèse : Gwénaël Jan Directeur de recherche UMR STLO INRA, Rennes Dir. de thèse : Vasco Azevedo Professeur Université fédérale du Minas Gerais, Brésil. Invité(s) Yves Le Loir Directeur de l’UMR STLO INRA, Rennes Gwennola Ermel Professeur Université de Rennes 1,Rennes UNIVERSIDADE FEDERAL DE MINAS GERAIS INSTITUTO DE CIÊNCIAS BIOLÓGICAS DEPARTAMENTO DE BIOLOGIA GERAL PROGRAMA DE PÓS-GRADUAÇÃO EM GENÉTICA Tese de Doutorado Papel da proteína de superfície SlpB na imunomodulação e adesão da linhagem probiótica Propionibacterium freudenreichii CIRM-BIA 129. Orientado: Fillipe Luiz Rosa do Carmo Orientadores: Prof./Dr. Vasco Ariston de Carvalho Azevedo Dr. Gwénaël Jan Belo Horizonte - Brasil Rennes - France 2018 THESE / AGROCAMPUS OUEST Sous le label de l’Université Européenne de Bretagne pour obtenir le diplôme de : DOCTEUR DE L'INSTITUT SUPERIEUR DES SCIENCES AGRONOMIQUES, AGRO-ALIMENTAIRES, HORTICOLES ET DU PAYSAGE Spécialité : Biochimie, Biologie moléculaire et cellulaire Ecole Doctorale : VAS (Vie-Agro-Santé) présentée par : Fillipe Luiz Rosa do CARMO La protéine de couche de surface SlpB assure la médiation de l’immunomodualtion et de l’adhésion chez le probiotique Propionibacterium freudenreichii CIRM-BIA 129. Thèse préparée à l’UMR Sciences et Technologies du Lait et l’OEuf, INRA-Agrocampus Ouest, Rennes Et L'Université Fédérale de Minas Gerais, l'Institut de Sciences Biologiques, Belo Horizonte Soutenue le 6 septembre 2018 devant la commission d’Examen Composition du jury : Prof. Aristoteles Goes Neto, Brésil, Rapporteur Muriel Thomas, DR, INRA MICALIS, Rapporteur Prof. Gwennola Ermel, Examinateur Prof. Nathalie Desmasures, Examinateur Prof. Benoit Foligné, Examinateur Prof. Françoise Nau, référent Agrocampus Ouest Yves Le Loir, DU de STLO, Membre invité Prof. Vasco Azevedo, Brésil, Directeur de thèse Gwénaël Jan, DR, INRA STLO, Directeur de thèse Fillipe Luiz Rosa do Carmo Papel da proteína de superfície SlpB na imunomodulação e adesão da linhagem probiótica Propionibacterium freudenreichii CIRM-BIA 129. Tese apresentada ao programa de Pós- Graduação em Genética do Departamento de Biologia Geral do Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais como requisito parcial para obtenção do título de Doutor em Genética. Orientadores: Prof. Vasco Ariston de Carvalho Azevedo Dr. Gwénaël Jan Belo Horizonte – Brasil Rennes - France 2018 “Vi veri universum vivus vici” “Pelo poder da verdade, eu, enquanto vivo, conquistei o universo” “Par le pouvoir de la vérité, j'ai, de mon vivant, conquis l'univers” Faust - Johann Wolfgang von Goethe ACKNOWLEDGEMENT AGRADECIMENTOS - Ao meu orientador brasileiro, Vasco Azevedo, pela oportunidade, por todo o aprendizado, ensinamento e, principalmente por acreditar em mim; - Ao meu orientador francês, Gwénaël Jan, por me receber como seu discípulo, pelos ensinamentos, amizade, pelas conquistas e por me fazer acreditar em mim; - A Yves Le Loir, por toda ajuda e pela acolhida em seu Instituto de Pesquisa; - Aos membros da banca pela disponibilidade em avaliarem este trabalho de Tese; - As equipes de pesquisa do INRA de Rennes, pela ajuda e disponibilidade; - À Pós-graduação em Genética, por todo o suporte na parte administrativa desse doutorado; - À escola de doutorado do Agrocampus Ouest – Rennes, por todo o suporte na parte administrativa desse doutorado cotutela; - As agências de fomento CNPq, CAPES e ao Programa Ciências sem Fronteiras pelo auxílio financeiro concedido no Brasil e na França durante este período de Tese; - A todos os membros do laboratório LGCM, aprendizados dentro e fora do laboratório e pelas conquistas, especialmente Iza, Brenda, Carol, Baiano, Elma e Alberto; - A “minha equipe”, Bárbara, Sara, Bruna, Alessandra, Emiliano, Caio e Maria Izabel pela amizade, apoio e por acreditarem em mim, vocês são maravilhos! - A equipe do “LIB”, Luísa, Juliana e Elder pelo apoio incondicional; - À minha família “francesa”, Houem, Song Huang, Floriane, Oumaima e Samira, vocês me fortaceleram nessa jornada e tem um lugar muito especial em mim. Eu tenho orgulho de sermos amigos; - Aos meus amigos, Matheus, Amir, Gleydson, Luciano, Marcelo, César, Felipe, Emanuel e Fernando e Bruno que me apoiaram em todos os momentos, de perto ou de longe. - Ao meu pai e minha mãe, que sempre serão meus ídolos, obrigado pelo apoio e amor incondicional em todos os momentos, vocês realmente são uma rocha! - Aos queridos irmãos Frederico, Francislene, Ana Flávia, obrigado por tudo; - Ao Théo, por me fazer companhia em todos os momentos; A minha esposa, Luciana, por despertar o amor em mim, por ser forte e sempre ser o meu apoio nos momentos difíceis. Você sempre acreditou em mim e me disse que meus sonhos seriam realizados. Você é um pedaço essencial de mim. Eu te amo muito! I REMERCIEMENTS Je remercie : - Vasco Azevedo, mon directeur de thèse brésilien, pour l’opportunité qu’il m’a donnée, de tout ce que j’ai appris avec lui, de son enseignement et, surtout, d’avoir cru en moi ; - Gwénaël Jan, mon directeur de thèse Français, de m’avoir accepté comme disciple, pour ses enseignements, son amitié, les réalisations accomplies et d’avoir réussi à me faire croire en moi ; - Yves Le-Loir, pour toute son aide et pour l’accueil que jai reçu dans son institut de recherche ; - Les membres du jury pour leur disponibilité à évaluer ce travail de thèse ; - Les équipes de recherche de l’INRA de Rennes, pour leur aide et leur disponibilité ; - Le programme de troisième cycle en génétique, pour tout son soutien dans la partie administrative de cette thèse de doctorat en cotutelle ; - L’École doctorale de l’Agrocampus Ouest – Rennes, pour tout son soutien dans la partie administrative de cette thèse de doctorat en cotutelle ; - Les organismes de financement CNPq, CAPES et le Programme Sciences sans Frontières pour toute l’aide financière que j’ai reçue au Brésil et en France pendant la durée de cette thèse ; - Tous les membres du laboratoire LGCM pour leur amitié, pour mes apprentissages au sein et en dehors de ce laboratoire, pour les réalisations accomplies, je remercie tout particulièrement Iza, Brenda, Carol, Baiano, Elma e Alberto; - « Mon équipe », Bárbara, Sara, Bruna, Alessandra, Emiliano, Caio et Maria Izabel de leur amitié, leur soutien et d’avoir cru en moi, vous êtes fantastiques ! - L’équipe des « LIB », Louise, Juliana et Elder pour votre soutien inconditionnel ; - Ma famille « Française », Houem, Song Huang, Floriane, Oumaima et Samira, vous m’avez rendu plus fort et vous occupez tous une place très particulière dans ma vie. Je suis fier d´être votre ami ; - Mes chers amis Matheus, Amir, Gleydson, Luciano, Marcelo, César, Felipe, Emanuel e Fernando e Bruno qui m’ont soutenu à tout moment, de près ou de loin. - Mon père et ma mère, qui seront toujours mes idoles, je vous remercie de votre soutien et de votre amour inconditionnel, vous êtes vraiment un roc pour moi ! - Mon cher frère Frederico et mes chères soeurs Francislene et Ana Flávia, merci pour tout ; - Théo, de m’avoir accompagné pendant tout ce temps ; Ma femme, Luciana, d´avoir éveillé l’amour en moi, d’être forte à mes côtés et d’avoir été mon soutien dans les moments difficiles. Tu as toujours cru en moi et dit que mon rêve se réaliserait. Tu m’es essentielle. Je t’aime ! II THESIS OUTPUTS Published or submitted articles DO CARMO, FILLIPE L. R.; CORDEIRO, BARBARA F., OLIVEIRA, EMILIANO R., RABAH, HOUEM., SILVA, SARA H., SAVASSI, BRUNA, FIGUEIROA, ALESSANDRA, FONSECA, CAIO., QUEIROZ, MARIA I., RODRIGUES, NUBIA M., SANDES, SÁVIO H.C., CANTINI, ÁLVARO N., LEMOS, LUISA., ALVES, JULIANA L.A., CAETANO., A. M. F., FERREIRA, ÊNIO., LE LOIR, YVES., JAN, GWÉNAËL., AZEVEDO, VASCO. Surface layer protein SlpB is involved in Propionibacterium freudenreichii CIRM-BIA 129 ability to prevent 5-FU-induced mucositis. (in submission) DO CARMO, FILLIPE L. R.; SILVA, WANDERSON M., TAVRES, GUILHERME C., IBRAIM, IZABELA C., CORDEIRO, BARBARA F., OLIVEIRA, EMILIANO R., RABAH, HOUEM., CAUTY, CHANTAL., SILVA, SARA H., CANÁRIO, MARCUS V., CAETANO, ANA C. B., SANTOS, ROSELANE G., CARVALHO, RODRIGO D.D.O., JARDIN, JULIEN., PEREIRA, FELIPE L., FOLADOR, EDSON L., LE LOIR, YVES., FIGUEIREDO, HENRIQUE C.P., JAN, GWÉNAËL., AZEVEDO, VASCO. Mutation of the surface layer protein SlpB has pleiotropic effects in the probiotic Propionibacterium freudenreichii 129. v. 9, p. 1-22, 2018 CORDEIRO, BARBARA F., OLIVEIRA, EMILIANO R.,SILVA, SARA H., SAVASSI, BRUNA, ACURCIO, LEONARDO B., LEMOS, LUISA., ALVES, JULIANA L.A., ASSIS, HELDER C., VIERA, ANGÉLICA, T., CAETANO., A. M. F., FERREIRA, ÊNIO., LE LOIR, YVES., JAN, GWÉNAËL., GOULART, LUIZ R., AZEVEDO, VASCO, CARVALHO, RODRIGO D.O., DO CARMO, FILLIPE L. R. Whey protein isolate-supplemented beverage fermented by Lactobacillus casei BL23 and Propionibacterium freudenreichii 138 in the prevention of mucositis in mice. v. 9, p. 1-18, 2018 DO CARMO, FILLIPE L. R.; RABAH, H.; CARVALHO, R. D. O.; GAUCHER, F.; CORDEIRO, B. F.; SILVA, S. H.; LOIR, Y. L.; AZEVEDO, V.; JAN, G. Extractable Bacterial Surface Proteins in Probiotic|Host Interaction. Frontiers in Microbiology, v.
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