June 25, 2009

Scientists find promising new TB target

U.S. scientists studying how sugar units form carbohydrate chains have pinpointed a promising way to target medicines against tuberculosis.

University of Wisconsin-Madison researchers working with components of the tuberculosis bacterium said they identified an unusual process by which the pathogen builds an important structural carbohydrate. In addition to its implications for human health, the researchers said the mechanism offers insight into a widespread, but poorly understood, basic biological function -- controlling the length of carbohydrate polymers.

Carbohydrate polymers are the most abundant organic molecules on the planet, and it's amazing that we don't know more about (how they) are made, said Professor Laura Kiessling. There's not much known about how length is controlled in these carbohydrate polymers.

The research team focused on an enzyme called GlfT2 that is responsible for building a critical carbohydrate component of the TB bacterial cell wall.

The GlfT2 enzyme is essential for bacterial survival and growth, but the scientists said it has never been targeted by potential treatment methods. They said knowing the enzyme has two binding sites -- one for each end of a growing carbohydrate -- makes it an especially appealing drug target candidate.

Kiessling, graduate students John May and Rebecca Splain, and postdoctoral fellow Christine Brotschi report their research in the early online edition of the Proceedings of the National Academy of Sciences.