Scientists uncover ‘misunderstood’ TB enzyme, opening possible new drug target


Daijiworld Media Network - New Delhi

New Delhi, Aug 18: Scientists studying the bacteria that causes tuberculosis (TB) have discovered that they may have misunderstood the function of a key gene, a finding that could reveal a potential new vulnerability in the pathogen.

The research team, led by biochemist Luiz Pedro Carvalho of the Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology in the US, published the findings on August 17 in the Proceedings of the National Academy of Sciences (PNAS).

Scientists have studied the TB bacterium extensively, particularly since its genetic sequence was mapped in 1998. Until now, they believed that the rv2531c gene produced an enzyme involved in making molecules essential for basic bacterial functions such as growth.

The new study suggests that the enzyme performs a very different role. Researchers found that it converts glutamate, a molecule present in cells, into GABA, another molecule that bacteria can use in metabolism or in responding to stressful conditions.

“What scientists thought we knew about this enzyme is just wrong, it acts in a completely different way. This expands our understanding of microbial metabolism and opens new avenues for targeting metabolic pathways in several pathogenic organisms,” Carvalho said in a press release.

Enzyme works at remarkable speed

Researchers found that the enzyme can remain dormant for extended periods but becomes highly active under suitable conditions. Once activated, it can convert nearly 70 molecules of glutamate every second.

“It’s just insane, it converts glutamate to GABA at a rate of 70 per second. It’s one of the quickest enzymes we have,” Carvalho said.

The discovery could be significant because TB bacteria are highly adept at surviving the hostile conditions inside the human body. The pathogen can also remain dormant for years before becoming active again.

If the rv2531c enzyme helps the bacteria cope with stressful conditions, researchers may eventually be able to target it with new drugs. However, scientists stressed that the discovery is still at an early stage.

The researchers have established that the enzyme behaves differently from what was previously understood, but further work is needed to determine precisely what role it plays inside TB bacteria and whether it can ultimately be exploited for drug development.

Could other TB genes be misunderstood?

The finding also raises the possibility that other genes in the TB bacterium may have been incorrectly characterised.

Carvalho said researchers still do not know what some of the natural products produced by such biological systems might ultimately do, stressing that their potential uses could be difficult to predict.

“This is a natural product, and we have no idea what it does,” he said, adding that such molecules could potentially lead to unexpected applications.

The discovery therefore offers not an immediate new TB treatment, but a fresh avenue for understanding the bacterium’s metabolism and identifying vulnerabilities that could eventually be exploited in the development of new therapies.

  

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