Novel mechanism may lead to better TB control

TERRIBLE SCOURGE: There were about 1.5 million TB-related deaths in the world in 2013 - about one death every 21 seconds.

A recent finding by scientists of a novel mechanism in which one of the proteins of Mycobacterium tuberculosis suppresses the adaptive immune response in the host could lead to development of new drugs to control the disease.

The team of scientists led by Dr. Sangita Mukhopadhyay, Group Leader, Laboratory of Molecular Cell Biology at the Centre for DNA Fingerprinting and Diagnostics (CDFD) has found that Mycobacterium tuberculosis protein ESAT-6 suppresses host’s protective functions. They identified that ESAT-6 directly binds with host molecule beta-2 microglobulin and inhibits antigen presentation to CD8 T-cells which play a key role in protective immune response mechanism of the host.

Dr. Sangita said the CD8 T-cells recognise the infected immune cells and directly kill them.

The ESAT-6 protein through its interaction with the host molecule would delay or inhibit the CD8 T-cells immune response, which was important to control the disease.

The novel mechanism involving the interaction between ESAT-6 and beta-2 microglobulin not only shed new light on host-pathogen relationship, but could open up new avenues for development of novel drugs or vaccine for TB therapy, she added.

Dr. Sangita said beta-2 micro globulin would be free to do its protective role once the interacting domain gets neutralised and the process would help in antigen presentation and activation of CD8 T-cells.

The work of the CDFD team was published in October 2014 issue of PLoS Pathogens .

The scientists are now planning to develop an ESAT-6-beta-2m crystal structure for designing of small molecule inhibitor. “Once that is done, we can go for in-vitro experiments initially and animal studies subsequently”, she added.

She said there was a need to develop newer drugs for TB in view of the growing incidence of multi-drug resistance to the disease.

Quoting WHO statistics, she said about 2.3 million cases occur annually in India, one-fifth of global incidence, with one death occurring every 23 seconds. It has also has one of the highest number of multi-drug-resistant patients.

As estimated by WHO, 300,000 people die from TB each year in India.

There were about 1.5 million deaths in the world in 2013 — about one death every 21 seconds.

It is estimated that about 40 per cent of Indians are infected with TB bacteria, the vast majority of whom have latent rather than active TB disease.