Genomic analysis of smooth tubercle bacilli provides insights into ancestry and pathoadaptation of Mycobacterium tuberculosis

Philip Supply (1) , Michael Marceau (1) , Sophie Mangenot (2) , David Roche (3, 2) , Carine Rouanet (1) , Varun Khanna (4) , Laleh Majlessi (5) , Alexis Criscuolo (6) , Julien Tap (6) , Alexandre Pawlik (4) , Laurence Fiette (7, 8) , Mickael Orgeur (4) , Michel Fabre (9) , Cécile Parmentier (4) , Wafa Frigui (4) , Roxane Simeone (4) , Eva C. Boritsch (4) , Anne-Sophie Debrie (10, 1) , Eve Willery (1) , Danielle Walker (11) , Michael A. Quail (11) , Laurence Ma (12) , Christiane Bouchier (12) , Grégory Salvignol (3, 2) , Fadel Sayes (5) , Alessandro Cascioferro (4) , Torsten C Seemann (13) , Valérie Barbe (14, 2) , Camille Locht (15, 1) , Maria-Cristina Gutierrez (1, 16) , Claude Leclerc (5) , Stephen D Bentley (11) , Timothy Stinear (17) , Sylvain Brisse (6) , Claudine Médigue (3, 2) , Julian Parkhill (11) , Stéphane Cruveiller (3, 2) , Roland Brosch (4)

1 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
2 CEA - Commissariat à l'énergie atomique et aux énergies alternatives
3 UMR 8030 - Génomique métabolique
4 Pathogénomique mycobactérienne intégrée
5 Régulation Immunitaire et Vaccinologie
6 PF8 - Génotypage des Pathogènes et Santé Publique (Plate-forme)
7 Histopathologie humaine et Modèles animaux
8 UVSQ - Université de Versailles Saint-Quentin-en-Yvelines
9 HIA Percy
10 Mécanismes moléculaires de la pathogénie microbienne
11 The Wellcome Trust Sanger Institute [Cambridge]
12 Génomique (Plate-Forme) - Genomics Platform
13 Victorian Bioinformatics Consortium [Clayton]
14 GENOSCOPE - Genoscope - Centre national de séquençage [Evry]
15 Mécanismes moléculaires de la pathogenèse bactérienne
16 Département Infection et Epidémiologie - Department of Infection and Epidemiology
17 University of Melbourne

Global spread and limited genetic variation are hallmarks of M. tuberculosis, the agent of human tuberculosis. In contrast, Mycobacterium canettii and related tubercle bacilli that also cause human tuberculosis and exhibit unusual smooth colony morphology are restricted to East Africa. Here, we sequenced and analyzed the whole genomes of five representative strains of smooth tubercle bacilli (STB) using Sanger (4-5× coverage), 454/Roche (13-18× coverage) and/or Illumina DNA sequencing (45-105× coverage). We show that STB isolates are highly recombinogenic and evolutionarily early branching, with larger genome sizes, higher rates of genetic variation, fewer molecular scars and distinct CRISPR-Cas systems relative to M. tuberculosis. Despite the differences, all tuberculosis-causing mycobacteria share a highly conserved core genome. Mouse infection experiments showed that STB strains are less persistent and virulent than M. tuberculosis. We conclude that M. tuberculosis emerged from an ancestral STB-like pool of mycobacteria by gain of persistence and virulence mechanisms, and we provide insights into the molecular events involved.

Domains: Life Sciences [q-bio]

Philip Supply, Michael Marceau, Sophie Mangenot, David Roche, Carine Rouanet, et al.. Genomic analysis of smooth tubercle bacilli provides insights into ancestry and pathoadaptation of Mycobacterium tuberculosis. Nature Genetics, 2013, 45 (2), pp.172-179. ⟨10.1038/ng.2517⟩. ⟨pasteur-02615220⟩