Structural studies shed light on TB treatments

29 March 2009


Mycobacterium TuberculosisTuberculosis, or TB, is a growing problem around the world, and it's on the rise in Western countries as well as in the developing world - it's thought that someone somewhere is being infected with TB every single second. Now researchers in the US have made a discovery that could help scientists to develop new drugs to tackle this growing problem.

Current TB treatments only tackle actively growing bacteria - the Mycobacterium tuberculosis that cause the disease. But these bugs can also lie low in the body - a property called latency - making them difficult to treat effectively. It's thought that around a third of the world's population has a latent infection with Mycobacterium tuberculosis, and one in ten of these will go on to develop full-blown TB.

Led by Barbara Gerratana at the University of Maryland, the researchers uncovered the molecular structure and mechanism of an enzyme called NAD+ synthetase, which plays an important role in the TB bacterium's energy production by producing a chemical called NAD+.

It's an important drug target, because while humans use many different molecular pathways to produce NAD+, the TB bacteria only use two, and they both rely on NAD+ synthetase. And the enzyme is still needed even if the bacteria are lying low, or latent. So knocking out the action of this enzyme using drugs could be a powerful and specific way to treat TB infections, including latent infections.

The researchers used a technique called X-ray crystallography to find the structure of NAD+ synthetase at an atomic scale. High-energy X-ray beams are fired through crystals made of the enzyme, and the resulting image is analysed by computer to reveal the structure.

Now we have this structure, it's going to be possible to rationally design drugs that specifically fit into crucial parts of the enzyme and block its activity. So it's a big step forward in the fight against TB infection.


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