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

2013; Nature Portfolio; Volume: 45; Issue: 2 Linguagem: Inglês

10.1038/ng.2517

1546-1718

Philip Supply, Michaël Marceau, Sophie Mangenot, David Roche, Carine Rouanet, Varun Khanna, Laleh Majlessi, Alexis Criscuolo, Julien Tap, Alexandre Pawlik, Laurence Fiette, Mickael Orgeur, M. Fabre, C Parmentier, Wafa Frigui, Roxane Siméone, Eva C. Boritsch, Anne‐Sophie Debrie, Eve Willery, Danielle Walker, Michael A. Quail, Laurence Ma, Christiane Bouchier, Grégory Salvignol, Fadel Sayes, Alessandro Cascioferro, Torsten Seemann, Valérie Barbe, Camille Locht, Maria-Cristina Gutiérrez, Claude Leclerc, Stephen D. Bentley, Timothy P. Stinear, Sylvain Brisse, Claudine Médigue, Julian Parkhill, Stéphane Cruveiller, Roland Brosch,

Bacteriophages and microbial interactions

Roland Brosch and colleagues report whole-genome sequencing of tubercle bacilli with smooth colony morphology, also known as Mycobacterium canetti and/or Mycobacterium prototuberculosis, obtained from humans with tuberculosis from geographically diverse regions. Their comparative genomic analysis with Mycobacterium tuberculosis and other M. tuberculosis complex members identifies extensive recombination and provides insights into the evolution of mycobacteria. The authors also report that tubercle bacilli with smooth colony morphology show reduced persistence and virulence compared to M. tuberculosis strains in infection experiments in mice. 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.