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Research teams led by Christophe Guilhot of the Institute of Pharmacology and Structural Biology (CNRS / Paul Sabatier University - Toulouse) and Roland Brosch of the Institut Pasteur, in collaboration with the team led by Carlos Martin of the University of Zaragoza (Spain), examined the mechanisms involved in tuberculosis (TB) transmission to explain why tubercle bacilli of animal origin don't spread within human populations. Their work, published on July 21, 2014 in the journal PNAS, opens up new possibilities for understanding the functions and mechanisms involved in TB transmission in humans and could eventually lead to therapeutic solutions for preventing the spread of this infectious agent.
TB is considered one of the most dangerous infectious diseases in the world, still causing over one million deaths each year. In humans, the disease is caused by a bacterium known as "Koch's bacillus" which spreads efficiently through aerosol. TB also affects a wide range of other mammals, but, despite having a genetic heritage very similar to that of the human strains, the animal strains of tuberculosis bacilli are very rarely involved in human-to-human transmission chains. By comparing the genomes of multiple strains, the scientists identified three mutations that were present in all of the animal strains but not in human strains. In experiments where these mutations were transferred to human tuberculosis bacilli, the virulence of these bacilli was significantly reduced in various cellular and animal models. This work explains why tubercle bacilli of animal origin have little impact on the epidemiology of the disease in human populations.
Illustration: © Institut Pasteur/Antoinette Ryter
Section of Mycobacterium bovis
Evolutionary history of tuberculosis shaped by conserved mutations in the PhoPR virulence regulator ; J. Gonzalo-Asensio, W. Malaga, A Pawlik, C. Astarie-Dequeker, C. Passemar, F. Moreau, F. Laval, M. Daffé, C. Martin, R. Brosch & C. Guilhot ; PNAS ; July 21, 2014.