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Tuberculosis (INCO)

Regulation of the Cell Cycle and Dormancy in Mycobacterium Tuberculosis
Framework programme:
Project number:
EC contribution:
€ 1 500 000
36 months
Starting date:
1 October 2001


Tuberculosis remains one of the most important infectious diseases, causing about 3 million deaths every year, the developing world accounting for the majority of cases. This disease is intimately linked to the pathogenesis of the causative agent, Mycobacterium. tuberculosis. This bacterium can lie quiescent in unidentified sites in the human host for years without producing overt disease and then revive to cause lesions and, in many cases, progressive tuberculosis. Bacterial genes that govern the latency state of the infection of M. tuberculosis will be identified and it will be established how they affect the cell cycle division. The project will seek to clarify the mechanism by which this bacteria shifts down to a dormant state and reverts to active growth again, and to describe morphologically and functionally the persistent M. tuberculosis cell. Association of IS6110 transpositions to dormancy will be assessed.


The aim of this project is to clarify the mechanisms by which tuberculosis shift down to dormant state and revert to active growth again. The specific objectives are:

1) to determine the influence of stress conditions (in vivo and in vitro) on the expression of the genes involved in active duplication, dormant state and resuscitation
2) to determine the expression of cell division genes as a function of the bacterial cell cycle
3) to determine the role of the genes previously identified by studying knockout mutant strains
4) to investigate the mechanisms involved that convert M. tuberculosis from an active growth to latency and vice versa
5) to determine the possible association of IS6110 transpositions and the evolutionary development of M. tuberculosis (dormancy and progressive disease).

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