University of Leicester eBulletin

Taming a Worldwide Killer

May 2002
No 106

University of Leicester scientists, together with collaborators at the University of Kent, have recently received a grant of £189,286 from the Wellcome Trust to continue ground-breaking research which, it is hoped, will contribute to the development of new ways of treating and preventing tuberculosis (TB).

With the deciphering three years ago of the complete genome of the bacterium responsible for TB in humans, the way became open to discovering how the disease is caused in humans and domestic animals.  

The Leicester research team, led by Dr Mark Carr of the Department of Biochemistry, is investigating a family of proteins (molecular machines) which are associated with the ability of the TB bacterium to infect people and also with the development of immunity to the disease.  

Dr Carr explained: “ Currently, there are about a dozen or so proteins from the TB bacterium where there is some clear link with immunity or infection. What we have done is focus on a few of these proteins to try to understand what they do and how they do it, which will allow us to take a more informed approach to new vaccine development and the selection of targets for new TB drugs.”

Dr Carr has no illusions about the importance of his research. Tuberculosis is a major infectious disease amongst humans, responsible for the deaths of about 3 million people annually, and is a growing world-wide problem. Nor is it confined to the developing world, with drug resistant strains of the TB bacterium becoming an increasing problem in both Western Europe and North America.  

He added: “If you walk around the streets of central London or New York you will probably be exposed to someone with active TB. Also, many people do not realise that TB has little respect for social standing or background, and in recent years in New York it has affected both Wall Street executives and people living on the streets.”

“TB is also closely linked to AIDS. If you have a depressed immune system the TB bacterium will readily take advantage, which is why it has re-emerged in Africa so strongly.”

He is, however, optimistic in the long term. “Within ten years we should have a more effective vaccine for TB, which represents the best hope for clearing the disease from the third world.”

The Wellcome Trust funding is the second grant the Leicester group has received from the Trust for this research. In addition it has received funding for students to work on the project from the BBSRC and Central Veterinary Laboratories. The project is a collaboration with Dr Richard Williamson at the University of Kent and with the TB Research Group at the Central Veterinary Laboratories (Dr Glyn Hewinson and Dr Stephen Gordon).

Factfile

·      The bacterium responsible for the disease in humans is Mycobacterium tuberculosis, which was one of the first organisms to have its complete instructions for life (genes) decoded. TB in cattle is caused by Mycobacterium bovis. The two bacteria are very closely related and it is now believed that humans were responsible for passing the disease to cattle rather than visa versa.

·      A major challenge for current and future scientific research in tuberculosis is to identify which of the almost 4000 sets of genes carried by M. tuberculosis are required for the bacteria to infect humans, and to understand what the proteins produced by these genes are doing and how. In the long term, this type of research will lead to the development of improved tuberculosis therapies and vaccines.

·      The Leicester research project supported by the Wellcome Trust is focused on a family of molecular machines (the ESAT-6/CFP-10 protein family), which appear to play a key role in the infection process and in the development of protective immunity.  

·      The currently available vaccine (BCG) uses a weakened strain of M. bovis to induce immunity. It is about 80% effective for people of Western European descent, but in the Indian subcontinent it offers virtually no protection at all, for reasons which are not yet understood.   

·      One third of the world’s population carries the TB bacterium, but only a small percent develop the disease.

·       M. tuberculosis is fairly closely related to the bacterium responsible for leprosy (Mycobacterium leprae) and so knowledge gained from biochemical studies of TB may well benefit the fight against leprosy.

·       The Central Veterinary Laboratories are part of DEFRA.

Note to editors: Further information is available from Dr Mark Carr, Department of Biochemistry, University of Leicester, telephone 0116 252 3054, email mdc12@le.ac.uk  

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