title: Insights on the emergence of Mycobacterium tuberculosis from the analysis of Mycobacterium kansasii.
abstract: By phylogenetic analysis, Mycobacterium kansasii is closely related to Mycobacterium tuberculosis. Yet, although both organisms cause pulmonary disease, M. tuberculosis is a global health menace, whereas M. kansasii is an opportunistic pathogen. To illuminate the differences between these organisms, we have sequenced the genome of M. kansasii ATCC 12478 and its plasmid (pMK12478) and conducted side-by-side in vitro and in vivo investigations of these two organisms. The M. kansasii genome is 6,432,277 bp, more than 2 Mb longer than that of M. tuberculosis H37Rv, and the plasmid contains 144,951 bp. Pairwise comparisons reveal conserved and discordant genes and genomic regions. A notable example of genomic conservation is the virulence locus ESX-1, which is intact and functional in the low-virulence M. kansasii, potentially mediating phagosomal disruption. Differences between these organisms include a decreased predicted metabolic capacity, an increased proportion of toxin-antitoxin genes, and the acquisition of M. tuberculosis-specific genes in the pathogen since their common ancestor. Consistent with their distinct epidemiologic profiles, following infection of C57BL/6 mice, M. kansasii counts increased by less than 10-fold over 6 weeks, whereas M. tuberculosis counts increased by over 10,000-fold in just 3 weeks. Together, these data suggest that M. kansasii can serve as an image of the environmental ancestor of M. tuberculosis before its emergence as a professional pathogen, and can be used as a model organism to study the switch from an environmental opportunistic pathogen to a professional host-restricted pathogen.
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada McGill International TB Centre, Montreal, Québec, Canada.
authors.forename: Joyce
authors.initials: J
authors.lastname: Wang
authors.affiliation: McGill International TB Centre, Montreal, Québec, Canada Research Institute of the McGill University Health Centre, Montreal, Québec, Canada.
authors.forename: Fiona
authors.initials: F
authors.lastname: McIntosh
authors.affiliation: McGill International TB Centre, Montreal, Québec, Canada Research Institute of the McGill University Health Centre, Montreal, Québec, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Radomski
authors.affiliation: McGill University and Génome Québec Innovation Center, Montreal, Québec, Canada.
authors.forename: Ken
authors.initials: K
authors.lastname: Dewar
authors.affiliation: Unit for Integrated Mycobacterial Pathogenomics, Institut Pasteur, Paris, France.
authors.forename: Roxane
authors.initials: R
authors.lastname: Simeone
authors.affiliation: Dynamics of Host-Pathogen Interactions Unit, Institut Pasteur, Paris, France.
authors.forename: Jost
authors.initials: J
authors.lastname: Enninga
authors.affiliation: Unit for Integrated Mycobacterial Pathogenomics, Institut Pasteur, Paris, France.
authors.forename: Roland
authors.initials: R
authors.lastname: Brosch
authors.affiliation: Microbial Evolutionary Genomics Unit, Institut Pasteur, Paris, France.
authors.forename: Eduardo P
authors.initials: EP
authors.lastname: Rocha
authors.affiliation: McGill International TB Centre, Montreal, Québec, Canada INRS-Institut Armand-Frappier, Laval, Québec, Canada frederic.veyrier@iaf.inrs.ca marcel.behr@mcgill.ca.
authors.forename: Frédéric J
authors.initials: FJ
authors.lastname: Veyrier
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada McGill International TB Centre, Montreal, Québec, Canada Department of Medicine, McGill University, Montreal, Québec, Canada frederic.veyrier@iaf.inrs.ca marcel.behr@mcgill.ca.
authors.forename: Marcel A
authors.initials: MA
authors.lastname: Behr
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D005260:Female; D016680:Genome, Bacterial; D023281:Genomics; D008810:Mice, Inbred C57BL; D019909:Mycobacterium kansasii / Q000145:classification / Q000235:genetics*; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D010641:Phenotype; D010802:Phylogeny; D014774:Virulence / Q000235:genetics
keywords: Mycobacterium kansasii; comparative genomics; mycobacteria; phylogeny; virulence