Molecular mechanisms of Streptococcus pyogenes tissue colonization and invasion Antonin Weckel To cite this version: Antonin Weckel. Molecular mechanisms of Streptococcus pyogenes tissue colonization and invasion. Microbiology and Parasitology. Université Sorbonne Paris Cité, 2018. English. NNT : 2018US- PCB097. tel-02984777 HAL Id: tel-02984777 https://tel.archives-ouvertes.fr/tel-02984777 Submitted on 1 Nov 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 Paris Descartes Ecole doctorale BioSPC Institut Cochin INSERM U1016 / Equipe Barrières et Pathogènes Molecular mechanisms of Streptococcus pyogenes tissue colonization and invasion By Antonin WECKEL PhD Thesis in Microbiology Directed by Agnès Fouet Thesis defense: 30th of October 2018 Jury members: Pr Anna NORRBY-TEGLUND Reviewer Dr Pascale SERROR Reviewer Pr François VANDENESCH Examiner Dr Philippe BOUSSO Examiner Dr Agnès FOUET PhD supervisor “We have to remember that what we observe is not nature herself, but nature exposed to our method of questioning” Werner Heisenberg Physics and Philosophy: The Revolution in Modern Science (1958) Acknowledgements I would like to thank Pascale Serror, Anna Norrby-Teglund, François Vandenesch and Philippe Bousso for having kindly accepted to be part of my defense jury, in particular to Anna Norrby- Teglund who came from Sweden for my defense. It has been 12 years now that I realized I want to work in life science research. Considering the beginning of my memories, this is more than half of my life having this idea stuck in my head. I want here to take the time to acknowledge all the people who contributed to this seed to grow into the doctor I’m about to become: the beauty of a flower resides less in the seed than in the quality of the environment it is exposed to during its growth. I consider that over the past years, I have been enlightened and watered by being surrounded by many wonderful people. While this dissertation and PhD are mine, this work belongs also to all of them. Thanks to Agnès and Claire for accepting me in the team and project. Agnès was a wonderful supervisor, always here when I needed her. I learned so much with her; she was a very good GPS during my PhD, I never felt lost and her directions were always correct. A very kind, upright and mindful boss. Thanks to Claire for always being kind and frank with me. Céline Méhats. Officially my “collaborator”. We had such a friendly and productive collaboration. You put so much energy into this project that started from nothing. You are a wonderful researcher and I am so glad I had the chance to work with you. Thanks to Thomas Guilbert. He gave me the knowledge, the curiosity, the will to work in microscopy. I never ever did microscopy before I met him and I still remember his first “lesson” on the microscope. He replied to several calls while I was such in a state in the L2 microscope during my night experiments. 9pm, 10pm. He was in bars, restaurants. He shouldn’t have replied. But I am so glad he did!! Thanks to Thierry Meylheuc for the SEM images. I will never forget the excitement of the first session with you, discovering the beautiful landscape of the infection at the nanometric level. Thanks to Magalie for all the help and support at the beginning of my PhD. Thanks to Samuel for being my biochemistry mentor and such a friendly colleague. Thanks to Constantin, my last year roommate, labmate, late evening-mate, weekend-mate and dissertation-mate. I am glad we had the opportunity to do our last year together, working next to you made everything easier to go through. Thanks to all past and current members of my team. Abdel, Asmaa, Anne-Sophie, Céline, Clara, Gerald, Julie and Lionel. A very nice environment and people to work in and with. Thanks to all the interns I had the chance or not to supervise. You learn a lot from your own mistakes, but also from those of others. Special thanks to Dorian, Quentin and Sandra. Thanks to the Donnadieu team. I owe you a lot, I had so much help and so many advice from all of you. I would not have done a 100th of what I did in microscopy without you. You always welcomed me and tried to help. Thanks to Elisa, Vincent, Emmanuel, Alain, Sarah, Chahrazade. Thanks to my former teacher and supervisors (Mr Poisson, Marie-Claude Serre, David Ermert and Anna Blom). You trusted me, and gave me all the knowledge and tools to start my PhD in the most comfortable way possible. Thanks to the people from the facilities I used during this PhD: Cybio, Proteomic facility and the Imag’IC facility. Thanks to Maryline Bajolle for her kindness and help. Thanks to Méchain building, Florian, Gaëlle, Christophe, Marina, Mickaël, Roy, Maxence, Ghina, Fanny, and all the people at the Institute I’ve been working for a couple of years . 1 Thanks to JeCCo and associates, Armelle, Stéphane, Marion, Gabrielle, Gabriel, Simon, Robin, Cyril, Mariangela, Rozenn, Anaïs, Vincent, Milica. Thanks for all this time releasing pressure from our day work and from the beer tap. I always think of Coralie, Béatrice, Nicolas and David as a special category of friends. We did secondary school together. I know them for more than 10 years. Thanks for all the time spent together and for being friends I wish to keep all my life. Who could have guessed while taking our daily lunch in the Agora we would ever be here for my PhD! ENS was a great opportunity on many aspects. Meeting Pierre, Aurélien, Noémie, Anne, Justine, Thomas, Valentine, Milena, Julia, Ralitza and Xavier was one of the best. So many parties, so many holidays and memories altogether. So much fun. Thank you all. Thanks to Mickael and Alex. Thanks for making me speak English and drinking beer on a regular base. You are true friends that always helped me through time of doubts. I have two brothers and a sister, Adrien, Amélie and Louis. I am so glad we had the opportunity to spend monthly time together for several years in Paris when we were reunited. Though we are no longer on the same continent, I know I have a wonderful family I can count on at any time in my life and this is invaluable. Thanks to all the members of my family, for their care and love, especially my godmother Corinne. Thanks to my grandfather for saying since I knew I wanted to do research: “A researcher who searches, it is easy to find, but a researcher who finds, we are still searching for them”. To which I used to reply in my innocent and naive youth and with a sense of humor: “I will not become a researcher, but a finder”. My parents definitely played a critical role in my calling to science. Though none is a scientist, I have been nurtured on science very early in life, and I will never ever be able to thank them sufficiently for that. They gave me all I needed to develop my curiosity and to have the best education. They kindly supported all my life decisions. My prepa was a difficult time not only for me but also for them, they bore and tolerated things many parents would not have. It was a time none of us regret, but I don’t know if they realize that I would not have done it without them. They have always trusted me, more than I ever did, or ever will trust myself. The further I get from childhood, the further I am from their life, the harder it is for me to retain tears thinking of my own mother not sleeping for me to grow up in the most suitable environment. I don’t know if anything can be worth what they did for me, but I want to thank them and dedicate this PhD to them. So far I described many “categories” of people that helped me over the past years. Coralie enters all categories: she has always been here for me and for a long time, she cared for me, she was here at any time of the day and night for my tears and my laughs, she helped me a lot to release the pressure from the lab. You tolerated my bad mood and accepted that I come and leave our sweet home in the middle of the night, and the following days when I was tired and unpleasant. Thank you. We did it, together, hand in hand. 2 Remerciements J’aimerais remercier Pascale Serror, Anna Norrby-Teglund, François Vandenesch et Philippe Bousso d’avoir gentiment accepté de faire partie de mon jury de thèse. Merci en particulier à Anna Norrby-Teglund qui a fait le déplacement depuis la Suède. Cela fait maintenant 12 ans que j’ai réalisé que j’aimerais travailler dans la recherche en biologie. En prenant compte de l’âge de mes premiers souvenirs, j’ai eu cette idée coincée dans ma tête durant plus de la moitié de ma vie. J’aimerais ici prendre le temps de remercier toutes les personnes qui ont contribué à faire de cette graine le docteur que je suis sur le point de devenir : la beauté d’une fleur réside moins dans la graine que dans l’environnement auquel elle est exposée durant sa croissance.