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Streptococcus Alexandre Miguel Santos Almeida Evolutionary insights into the host–specific adaptation and pathogenesis of group B Streptococcus Alexandre Miguel Santos Almeida To cite this version: Alexandre Miguel Santos Almeida. Evolutionary insights into the host–specific adaptation and patho- genesis of group B Streptococcus. Microbiology and Parasitology. Université Pierre et Marie Curie - Paris VI, 2017. English. NNT : 2017PA066029. tel-01599269 HAL Id: tel-01599269 https://tel.archives-ouvertes.fr/tel-01599269 Submitted on 2 Oct 2017 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 Pierre et Marie Curie (Paris 6) Ecole Doctorale: Complexité du Vivant Thèse présentée par Alexandre Miguel Santos Almeida pour obtenir le grade de Docteur Evolutionary insights into the host-specific adaptation and pathogenesis of group B Streptococcus Soutenance prévue le 31 mars 2017. Jury composé de: Prof. Philippe Lopez Université Paris VI Président Dr Immaculada Margarit GSK Vaccines Rapporteur Prof. Ivan Matic Université Paris V Rapporteur Dr Christine Citti CNRS, INRA Examinateur Dr Olivier Tenaillon CNRS, IAME, Université Paris VII Examinateur Dr Philippe Glaser Institut Pasteur Directeur de these Université Pierre et Marie Curie (Paris 6) Doctoral School: Complexité du Vivant Thesis presented by Alexandre Miguel Santos Almeida for the degree of Doctoral of Philosophy Evolutionary insights into the host-specific adaptation and pathogenesis of group B Streptococcus Defence planned for March 31, 2017. Jury composition: Prof. Philippe Lopez Université Paris VI President Dr Immaculada Margarit GSK Vaccines Reviewer Prof. Ivan Matic Université Paris V Reviewer Dr Christine Citti CNRS, INRA Examiner Dr Olivier Tenaillon CNRS, IAME, Université Paris VII Examiner Dr Philippe Glaser Institut Pasteur Thesis supervisor “There is grandeur in this view of life, with its several powers, having been originally breathed into a few forms or into one; and that, whilst this planet has gone cycling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have been, and are being, evolved.” — Charles Darwin AcknoWledgements The collaborations and relationships developed With so many people during my PhD were crucial for accomplishing this Work. First of all I Would like to thank my supervisor Philippe Glaser for having given me the opportunity to Work in his team and for being an exemplary PhD mentor. With his relentless curiosity and creative mind, Philippe constantly challenged me With neW ideas to drive the project forward. Most importantly, he Was a good friend throughout these years, caring and understanding when needed, always ready to give helpful advice. I would also like to give a special thanks to Isabelle Rosinski-Chupin, the other member of our team Who folloWed me closely through these years. Her hard working attitude and critical thinking inspired me to become a better scientist by having a more open mind and being more cautious and critical about my results. I have to give a shout-out to all the other former and present members of the unit Ecologie et Evolution de la Résistance aux Antibiotiques (EERA), especially Alexandre Lecomte, Anita Annamalé, Dimitri Desvillechabrol, Elisabeth Sauvage, Nicolas Cabanel, Olivia Dowding, Pierre-Emmanuel Douarre, Rafael Patiño-Navarrete and Romain Guérillot. In some Way or another they have all helped me during my stay and created a Welcoming and friendly environment to Work in. A special thank you to all our collaborators, especially the teams of Claire Poyart, Fernando Tavares and Ilda Sanches, Who Were instrumental in providing the right resources and expertise to carry out this Work. I would like to thank in particular Claire Poyart’s team at the Institut Cochin and the Centre National de Référence des Streptocoques (CNR-Strep) for insightful scientific discussions and for providing access to a valuable set of clinical samples that Were crucial to my PhD project. Thank you also to Adrien Villain for getting me started in the World of bioinformatics and to Christiane Bouchier and Laurence Ma for their invaluable service at the Genopole sequencing platform. I also thank the teams of Carmen Buchrieser and Patrick Trieu- Cuot, for the useful feedback, advice and help provided. 7 I thank the Pasteur-Paris International PhD Program and the ANR LaBex IBEID for the funding and opportunity to develop my PhD project at the Institut Pasteur. On a more personal level, I have to thank my partner in crime and the most important person in my life, Ana Silva. I thank her for her love and care, for being With me during the highs and loWs and for having taken the courage to come With me on this journey. Thank you to all my colleagues from the Pasteur PhD program and to the Portuguese community at the Institut Pasteur. A special thanks to Jovana Mihajlovic, Madhura Mukhopadhyay and Marisa Oliveira for all the fun and relaxing times We had to balance the hardships of everyday life. And last, but not least, to all my friends and family back in Portugal Who folloWed me on this endeavour from afar. I have to give a very special thanks to my parents and sister who supported me most closely on this personal venture. 8 Table of contents List of abbreviations .................................................................................................................... 11 List of figures ................................................................................................................................. 13 List of tables ................................................................................................................................... 13 Abstract ............................................................................................................................................ 15 Résumé ............................................................................................................................................. 17 Introduction ................................................................................................................................... 19 1. The host generalist pathogen Streptococcus agalactiae ........................................................ 20 1.1. Neonatal disease ............................................................................................................................ 21 1.2. Bovine mastitis ............................................................................................................................... 23 1.3. Disease in other hosts .................................................................................................................. 25 1.4. Colonization and virulence factors ........................................................................................ 26 1.4.1. Surface polysaccharides ..................................................................................................... 26 1.4.2. Surface and secreted proteins ......................................................................................... 27 1.4.3. Gene regulation ...................................................................................................................... 31 1.4.4. Transporters and antibiotic resistance ....................................................................... 33 1.5. Population structure and host specificities ........................................................................ 35 1.5.1. From capsular to Whole-genome typing ..................................................................... 35 1.5.2. Clinical and host association ............................................................................................ 37 2. Genomics of bacterial evolution and adaptation ...................................................................... 40 2.1. Phylogenetic and population genomic methods .............................................................. 40 2.1.1. General concepts of molecular evolution ................................................................... 40 2.1.2. Phylogenetic inference ....................................................................................................... 43 2.1.2.1. Maximum likelihood and Bayesian methods ........................................................ 47 2.1.2.2. Estimating the evolutionary rate ................................................................................ 49 2.1.3. Detecting natural selection ............................................................................................... 50 2.2. Within-host diversity and evolution ..................................................................................... 51 2.2.1. Transition from carriage to infection in opportunistic pathogens .................. 53 2.2.2. Emergence of antibiotic resistance ............................................................................... 54 2.2.3. Transmission and recurrent infections ....................................................................... 55 2.3. Host adaptation
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