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Tuberculosis: discovery of a critical stage in evolution of the bacillus towards pathogenicity

It is the disappearance of a glycolipid from the bacterial envelope during evolution that may have considerably increased the virulence of tuberculosis bacilli in humans. Scientists from CNRS, Institut Pasteur and Université Toulouse III – Paul Sabatier1 have shown that this disappearance modified the surface properties ofMycobacterium tuberculosis, favoring its aggregation in a "cord" and increasing its pathogenicity. These findings, which enable a clearer understanding of the mechanisms linked to the evolution and emergence of tuberculosis bacilli, constitute a major advance in our knowledge of this disease. They are published in Nature Microbiology on 27 January 2016.

 

Tuberculosis is a chronic bacterial disease caused by the infective agentMycobacterium tuberculosis. In 2014, 9.6 million cases of tuberculosis and 1.5 million deaths were recorded throughout the world, meaning that this disease ranks second among causes of death from a single infective agent (WHO, 2015). To fight this disease, it is necessary to better understand the factors and mechanisms that favor its spread.

The evolutionary stages, and their associated genetic adaptations, that enabled the tuberculosis bacillus to colonize humans are still little understood, unlike those of other infectious diseases such as plague or typhus. To address this issue, the scientists focused on another bacillus,Mycobacterium canettii, which is known to cause a rarer type of tuberculosis and to be genetically close to the ancestor of M. tuberculosis. The team observed that colonies2 of these bacteria differed markedly from those of tuberculosis bacilli; while on a solid medium theM. tuberculosis colonies were dry, rough and wrinkled, those of M. canettii were smooth and viscous. In a liquid culture medium, the former were markedly aggregated in a cord form, while the latter were completely separate.

By studying spontaneous mutants of M. canettii forming wrinkled colonies, the scientists found that the change in appearance of these colonies was caused by a recombination between two genes involved in the production of a bacterial cell wall glycolipid. By focusing specifically on the genetic organization of this region in tuberculosis bacilli, they were able to demonstrate that a similar recombination had occurred in the ancestor of M. tuberculosis. This recombination led to inactivation of the biosynthetic pathway for the glycolipid and hence its disappearance from the surface of the bacilli. The scientists showed that in M. canettii, this disappearance modified the surface properties and thus favored its aggregation in a "cord", in the same way as in M. tuberculosis. Finally, by using different animal and cell models of infection, the team established that this modification to the bacterial envelope triggered a change in interactions with host defense cells and an increase in the virulence of M. canettii.

 

This discovery constitutes an essential stage in understanding the origin and emergence of the tuberculosis bacillus. The scientists will now continue studying M. canettii and M. tuberculosis in order to determine the bacterial factors, and immune responses induced by these factors, which have contributed to the success of M. tuberculosis as a major pathogen in humans.

 

1 From the Institut de Pharmacologie et de Biologie Structurale (CNRS/Université Toulouse III - Paul Sabatier), the Unité Pathogénomique Mycobactérienne Intégrée at Institut Pasteur and the Centre d’Infection et d’Immunité de Lille (CNRS/Inserm/Université Lille 1/Université Lille 2), as well as a scientist from Melbourne University, Australia. 
2 A colony is a mass of cells or micro-organisms that grows in a culture medium, which may be solid or liquid.

 

tuberculosis.jpg

On a solid culture medium, the colonies of M. canettii are smooth and sticky while those of M. tuberculosis are dry, rough and wrinkled © Roland Brosch, Institut Pasteur.

Bibliography 

Pks5 recombination-mediated surface remodelling in Mycobacterium tuberculosis emergence. Eva C. Boritsch, Wafa Frigui, Alessandro Cascioferro, Wladimir Malaga, Gilles Etienne, Françoise Laval, Alexandre Pawlik, Fabien Le Chevalier, Mickael Orgeur, Laurence Ma, Christiane Bouchier, Timothy P. Stinear, Philip Supply, Laleh Majlessi, Mamadou Daffé, Christophe Guilhot, et Roland Brosch. Nature Microbiology, 27 January 2016. DOI : NMICROBIOL.2015.19

 

Contacts 

Institut Pasteur scientist l Roland Brosch l T 01 45 68 84 46/06 80 92 48 52 l roland.brosch@pasteur.fr 
CNRS scientist l Christophe Guilhot l T 05 61 17 58 45/06 46 41 38 12 l Christophe.Guilhot@ipbs.fr 
CNRS press l Alexiane Agullo l T 01 44 96 43 90 l alexiane.agullo@cnrs-dir.fr 
IPBS press | Françoise Viala | M 06 01 26 52 59 | communication@ipbs.fr