Indian researchers identify gene that helps TB bacterium survive in human body

New Delhi,UPDATED: Dec 26, 2023 13:26 IST

Researchers at the Indian Institute of Science (IISc) have made a significant discovery in the fight against tuberculosis (TB).

They have identified a gene that plays a crucial role in the survival and persistence of Mycobacterium tuberculosis (Mtb) within the human host. This finding, published in Science Advances, could lead to new strategies for combating the disease that remains one of the top 10 causes of death worldwide.

The research team, led by Amit Singh, Associate Professor at the Department of Microbiology and Cell Biology, focused on understanding how Mtb can remain dormant in the body for extended periods.

Mayashree Das, a PhD student involved in the study, explained that while the immune system can often detect and eliminate Mtb, the bacterium has developed ways to hide and persist in oxygen-poor regions of the lungs, evading both the immune response and TB medications.

Singh's group cultivated Mtb in a Bio Safely Level-3 facility at IISc's Center for Infectious Disease Research, examining the bacterium's reliance on iron-sulphur clusters. These clusters are vital for various cellular processes, including respiration and energy production, which enable Mtb to survive the hostile environment of the lungs and cause infection.

The researchers discovered that the production of these iron-sulphur clusters is primarily controlled by a single gene known as IscS under normal and low-oxygen conditions.

However, when the bacterium is under oxidative stress, another set of genes, the SUF operon, is activated to meet the increased demand for new clusters.

By creating a mutant Mtb strain lacking the IscS gene, the team observed that its absence led to a severe form of the disease in mouse models, rather than the typical persistent, chronic infection. This suggests that the IscS gene regulates the SUF operon, maintaining a balance that allows the bacterium to persist in the host.

Furthermore, the mutant bacteria were found to be more susceptible to certain antibiotics, indicating potential new avenues for treatment. The researchers propose that targeting the IscS and SUF systems with a combination of antibiotics might enhance treatment efficacy.

This discovery not only sheds light on the mechanisms of TB persistence but also opens up possibilities for developing therapies aimed at eradicating the disease.

With continued research, the insights gained from the IISc study could eventually lead to the elimination of TB as a global health threat.