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Insights on the Emergence of Mycobacterium tuberculosis from the Analysis of Mycobacterium kansasii

Wang, Joyce; McIntosh, Fiona; Radomski, Nicolas; Dewar, Ken; Simeone, Roxane; Enninga, Jost; Brosch, Roland; Rocha, Eduardo P.; Veyrier, Frédéric; Behr, Marcel A. (2015). Insights on the Emergence of Mycobacterium tuberculosis from the Analysis of Mycobacterium kansasii Genome Biology and Evolution , vol. 7 , nº 3. p. 856-870. DOI: 10.1093/gbe/evv035.

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Résumé

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 genomeis 6,432,277 bp, more than 2Mb 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/6mice, 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.

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Mots-clés libres: mycobacteria phylogeny comparative genomics virulence Mycobacterium kansasii slowly growing mycobacteria esx-1 secretion system nontuberculous mycobacteria numerical classification pulmonary tuberculosis subsystems technology microbial genomes bovis bcg virulence infection
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 09 mars 2016 16:12
Dernière modification: 11 janv. 2017 20:44
URI: http://espace.inrs.ca/id/eprint/3275

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