The molecular players of tuberculosis

Tuberculosis is caused by Mycobacterium tuberculosis and its secret of survival is that it is capable of evading immune responses by hiding and multiplying in host macrophages. It is the leading cause of mortality by a single bacterial infection, killing almost 2 million people around the globe every year.

Autophagy is one of the many strategies used by M. tuberculosis to thwart antibacterial defences. A well-characterised cellular process involving the degradation of cytoplasmic components by lysosomes, autophagy is central for pathogen destruction. Experimental reports show that induction of autophagy in macrophages kills M. tuberculosis. However, the precise mechanism by which M. tuberculosis regulates autophagy and its role in pathogenesis remains largely unknown.

The EU-funded AUTOPHAGTUBERCULOSIS (Molecular mechanisms of autophagy regulation in tuberculosis) project has successfully gained further insight into the association of mycobacterial pathogenicity and autophagy. To achieve this, scientists investigated autophagy molecules regulated by M. tuberculosis and identified novel factors that modulate autophagy.

Using microbiological, biochemical and fluorescence confocal microscopy, researchers observed that pathogenic mycobacterial species promote lesser recruitment of the classical autophagy marker LC3 than non-pathogenic mycobacteria.

AUTOPHAGTUBERCULOSIS project's main results indicate that the host's autophagic responses vary in mechanism and intensity according to the stage of infection. Through study of various mutants, and depending on the species, there are at least two mechanisms in play that are triggered by mycobacteria.

One involves phagosomal membrane damage and ubiquitin coating and a second independent process that needs to be completely characterised. The research also uncovered that modulation of autophagy is controlled by some non-protein elements in the bacterial cell envelope.

Overall, the results of the present study should shed light into the complex relationship between autophagy and M. tuberculosis. This could help in uncovering novel potential drug targets to reinstate autophagy in macrophages and kill this deadly pathogen.