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Scientists leading the way in TB cure

Scottish Scientists have made a key discovery which brings them ever closer to finding a cure for tuberculosis (TB) – the contagious disease which currently affects one third of the population of the planet.

Professor Jim Naismith of the University of St Andrews, in collaboration with fellow scientists in the USA, has been awarded funding by The National Institutes of Health (NIH) in the USA, to continue in the development of new antibiotics against TB.

Professor Naismith, a structural biologist at the University’s Centre for Biomolecular Sciences, is collaborating with Professor Richard Lee, a medicinal chemist from the University of Tenesee and Professor Mike McNeil, an expert in Mycobacteria tuberculosis at the University of Colorado.

“Tuberculosis is not easy to treat, and even normal TB requires a multidrug six month regimen,” said Professor Naismith.

“However, dangerous new strains of TB which are resistant to the combined drug treatment have been appearing, and the great fear is that multidrug resistant TB (MDR- TB) will become more common. Outbreaks of MDR-TB have been reported in New York and London, and it is fairly common in the former Soviet Union. MDR-TB is very difficult to treat, the second line drugs against TB are expensive and often have severe side effects. There is a pressing need for new antibiotics,” he continued.

The organism Tuberculosis (TB) results from infection with Mycobacteria tuberculosis, and like a common cold, it spreads through the air. Worldwide, TB is responsible for more disease and death than any other organism. According to the World Health Organisation (WHO), Tuberculosis kills approximately 2 million people each year and in 1993, they took the unprecedented step of declaring tuberculosis a global emergency, so great was the concern about the modern TB epidemic.

The latest figures issued by WHO estimate that between 2002 and 2020, approximately 1000 million people will be newly infected, over 150 million people will get sick, and 36 million will die of TB – if control is not further strengthened.

The $200,000 NIH funding will allow Professor Naismith and his collaborators to develop new compounds against TB.

A crucial series of discoveries were made by Professor Naismith and his St Andrews’ research group during Wellcome Trust-funded research, when they mapped out the structures of the proteins that make rhamnose in M. tuberculosis. Rhamnose is a sugar, which is not found in humans but in bacteria.

Professor McNeil proved that without rhamnose, Mycobacteria tuberculosis dies. Working together Professors Naismith, Lee & McNeil tried to predict what molecules would stop rhamnose being made in TB, Professor Lee’s group made several compounds and Professor McNeil’s tested them in the test tube. Some of those inhibitors worked in the test tube.

Chang Jiang Dong in Professor Naismith’s group determined the structure of the one of the rhamnose synthesising protein bound to the inhibitor. This structure allowed Professors Lee, McNeil and Naismith to design a second generation of potential drugs. Some of these second generation compounds have already been found to work in the test tube and to kill the whole bacteria. The NIH funding will allow the group to further develop these second generation compounds, with the aim of making them more potent.

“When we began our research, we hoped at some point to help treat TB,” said Professor Naismith

“TB is a terrible disease and we are keen to make progress against it. That our work in St Andrews is now being used so directly to help develop new drugs against TB is very exciting for everyone in the lab,” said Professor Naismith.

ENDS

NOTE TO EDITORS:

PROFESSOR NAISMITH IS AVAILABLE FOR INTERVIEW TODAY ON TELEPHONE 01334 463792 / 467245 OR EMAIL naismith@st-and.ac.uk

Issued by Beattie Media On behalf of the University of St Andrews Contact Gayle Cook on 01334 467227, mobile 07900 050103, or email gec3@st-andrews.ac.uk Ref: J Naismith TB grant pr300902 View the latest University news at http://www.st-andrews.ac.uk

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