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The emergence of the tuberculosis pathogen from its ancestral environmental progenitor is evolutionarily very recent

Philip Supply, CNRS Research Director, and his group members from the Center of Infection and Immunity of Lille, have recently co-led a study recently published in Nature Communications, entitled “A smooth tubercle bacillus from Ethiopia phylogenetically close to the Mycobacterium tuberculosis complex". This study involved collaborators from the Public Health Institute in Ethiopia and the San Raffaelle Institute in Italy.

Our previous work has suggested that the tuberculosis agents, included in the Mycobacterium tuberculosis complex, evolved from a progenitor clone that probably emerged from an ancestral pool resembling extant strains of M. canettii. The latter strains, almost exclusively obtained from tuberculosis patients from East Africa, are exceptional and represent early branches in the evolution of tuberculosis bacilli.

The new study describes the discovery and comparative genomic analysis of a new exceptional clinical isolate, obtained from an Ethiopian patient with tuberculosis. The results show that this strain shares the canonical phenotypic and genomic properties of M. canettii strains, but represents a phylogenetic branch much closer to the Mycobacterium tuberculosis complex than previously known M. canettii strains. Analysis of genomic traces of horizontal gene transfers, in this isolate and other strains of M. canettii, indicate the persistence (albeit at a reduced rate) of genetic exchanges in ancestral branches close to the emergence of the M. tuberculosis complex, suggesting the maintenance of interactions with an environmental microbiome prior to this emergence.

These new results indicate that the emergence of the ancestral progenitor of M. tuberculosis is evolutionarily much more recent than previously assumed.  They also suggest the existence, along the Great Rift Valley, of a continuum of strains derived from ancestral stages close to the original root of the tuberculosis pathogen. Moreover, these findings suggest the possibility of (re-)emergence of a new prototype of a professional tuberculosis pathogen.