Mycobacterium prototuberculosis

Mycobacterium is the single genus in the family Mycobacteriaceae, which belongs to the order Actinomycetales and the phylum Actinobacteria. This genus is divided into two main groups, including slowly and rapidly growing species, respectively. The tubercle bacillus, Mycobacterium tuberculosis, is the prototype of the first group. This bacterium is of high medical interest, as it is the causative agent of tuberculosis, one of the most devastating human disease. M. tuberculosis still causes about 9 millions of new tuberculosis cases and 2 millions deaths each year, and has infected over one third of the world human population.

Despite intensive research, the molecular bases of this evolutionary success remain unknown. This pathogen and its close relatives sum up in a single, genetically compact bacterial group, the origin of which was unidentified. It was recently discovered that human tubercle bacilli from East Africa represent extant bacteria of a much broader progenitor species, named M. prototuberculosis, from which the M. tuberculosis clonal group evolved.

This project aims at sequencing the genomes of 4 strains of these bacteria, representing the most distant groups of M. prototuberculosis identified so far. These tubercle bacilli were all isolated from human clinical cases. Unlike M. tuberculosis however, these strains display a smooth colony morphology, when grown on culture plates (Fig. 1A & 1B).

Also in contrast with classical tubercle bacilli, these strains are able to exchange parts of their genome with other strains, a process that is known to play a crucial role in adaptation of pathogens to their hosts.

The goal of this project is to analyse and compare the genomes of these 4 distant strains of M. prototuberculosis with those of M. tuberculosis strains in order to:

 identify specific genome regions and evolutionary factors that may have contributed to the success of M. tuberculosis as a pathogen.
 to understand how the M. tuberculosis genome has been assembled from its ancestral genetic pool
 to re-define the extent of diversity of the tubercle bacilli

These findings may lead to development of new diagnostic, preventive and therapeutic applications against tuberculosis.