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

Philip Supply, Michael Marceau, Sophie Mangenot, David Roche, Carine Rouanet, Varun Khanna, Laleh Majlessi, Alexis Criscuolo, Julien Tap, Alexandre Pawlik, Laurence Fiette, Mickael Orgeur, Michel Fabre, Cecile Parmentier, Wafa Frigui, Roxane Simeone, Eva C Boritsch, Anne-Sophie Debrie, Eve Willery, Danielle WalkerMichael A Quail, Laurence Ma, Christiane Bouchier, Gregory Salvignol, Fadel Sayes, Alessandro Cascioferro, Torsten Seemann, Valerie Barbe, Camille Locht, Maria-Cristina Gutierrez, Claude Leclerc, Stephen D Bentley, Timothy Paul Stinear, Sylvain Brisse, Claudine Medigue, Julian Parkhill, Stephane Cruveiller, Roland Brosch

Research output: Contribution to journalArticleResearchpeer-review

164 Citations (Scopus)

Abstract

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 (4-5x coverage), 454/Roche (13-18x coverage) and/or Illumina DNA sequencing (45-105x 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.
Original languageEnglish
Pages (from-to)172 - 179
Number of pages8
JournalNature Genetics
Volume45
Issue number2
DOIs
Publication statusPublished - 2013

Cite this

Supply, P., Marceau, M., Mangenot, S., Roche, D., Rouanet, C., Khanna, V., Majlessi, L., Criscuolo, A., Tap, J., Pawlik, A., Fiette, L., Orgeur, M., Fabre, M., Parmentier, C., Frigui, W., Simeone, R., Boritsch, E. C., Debrie, A-S., Willery, E., ... Brosch, R. (2013). Genomic analysis of smooth tubercle bacilli provides insights into ancestry and pathoadaptation of Mycobacterium tuberculosis. Nature Genetics, 45(2), 172 - 179. https://doi.org/10.1038/ng.2517