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Coming soon: A new therapy to combat TB?

Scientists have paved the way for the development of new drug therapies for tuberculosis by characterising the unique structure and mechanism of an enzyme in the bacterium that causes the disease.

world Updated: Mar 28, 2009 16:13 IST

Scientists have paved the way for the development of new drug therapies for tuberculosis by characterising the unique structure and mechanism of an enzyme in the bacterium that causes the disease.

“The NAD+ synthetase enzyme that our study describes is absolutely essential for the survival of the tuberculosis bacteria and an important drug target.

“We can now use the information we have about its structure and mechanism to develop inhibitors for this enzyme,” according to Barbara Gerratana, who led a team at Maryland University.

The study’s findings have been published in ‘Nature Structural & Molecular Biology´ journal.

In fact, the development of new drugs to combat TB has become urgent, as strains of TB resistant to all major anti-TB drugs have emerged worldwide.

According to other leading TB researchers, these new findings from Gerratana and her colleagues will be extremely valuable for the design of structure-based inhibitors specific for M tuberculosis NAD+ synthetase and may lead to the development of new drugs to combat and eliminate the disease.

"NadE (NAD+ synthetase) represents one of a small handful of TB drug targets that has iron-clad validation, the lack of a crystal structure was the only serious impediment to drug development and this study represents a hugely important step forward.

"Inhibiting NadE even kills non-replicating cells, so this discovery may well benefit the one-third of the human population that carries latent bacteria," said Clifton Barry, Chief of the Tuberculosis Research Section of the Intramural Research Division of the National Institute of Allergy and Infectious Diseases.

Unlike in humans, however, there are only two pathways involved in producing NAD+ in the tuberculosis bacterium and both depend on the activity of NAD+ synthetase to obtain NAD+.

"We are optimistic about the potential for developing new drugs that will effectively target this enzyme in TB and minimise side effects to humans, since we have NAD+ biosynthetic pathways that are independent of the NAD+ synthetase activity," Gerratana said.