Virulence of TB strain in Leicester outbreak caused by 'unusual' mechanism

Scientists identify mechanism that contributes to the virulence of a particular strain of tuberculosis - News Release

Issued by the Wellcome Trust

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23.00 BST
Monday 2 October 2006

Scientists have identified a mechanism that contributes to the virulence of a particular strain of tuberculosis, making it appear more likely to lead to disease than other strains. In 2001, this strain, known as CH, was responsible for a major school outbreak of TB in Leicester thought to have infected at least 254 pupils.

In general, most people infected with Mycobacterium tuberculosis, the bacterium that causes TB, will not show any symptoms. It is thought that one third of all people carry the bacteria, yet less than one in ten will develop TB. However, almost a quarter of the people infected with the CH strain required treatment for the disease. Left untreated, TB can prove fatal.

Now, a team jointly led by Dr Robert Wilkinson   at the Wellcome Trust Centre for Clinical Tropical Medicine, Imperial College London, and Professor Mike Barer at the University of Leicester, has identified a segment of the CH genome which, when absent, modifies the immune system’s response to the strain and make it more likely to lead to disease. The findings of their research are published today in the journal Proceedings of the National Academy Sciences of the USA. The research was funded by the Wellcome Trust and the Medical Research Council.

"Whilst this particular strain of TB does not appear more infectious than others, it appeared more likely to cause primary disease and endanger the health of an infected person," says Dr Wilkinson. "The CH strain has evolved a mechanism to avoid the early immune response and thus give it an advantage in the early struggle against the immune system. Interestingly the genetic basis for this appears to be the loss, rather than gain, of a gene, which is unusual."

The missing segment is thought to be have been deleted during a rare rearrangement within the CH genome.

"TB and other mycobacteria appear to be remarkably careless about preserving their genomes and appear to have evolved by a succession of 'accidents' in which several genes have been lost at a time," explains Professor Barer. "We don't really understand how the losses occur, but it is likely that, for one reason or another, loops form in the DNA and the genes in the loops are lost.

"Unlike many other bacteria, the TB group cannot pick up DNA from its relatives so it cannot get lost genes back again. The ultimate example of this is the leprosy bacillus. This has lost so many genes that it can now only grow in the tissues of humans, nine-banded armadillos and immunocompromised mice."

Despite the increased likelihood that the CH strain of tuberculosis will develop to the disease stage, Dr Wilkinson is keen to stress that it is still possible to treat the strain.

"Although this strain appears more likely to lead to disease than others, it is responsive to the antibiotics prescribed for TB infection," says Dr Wilkinson.

Professor Barer comments: "Our studies on the TB outbreak strain seem to have uncovered a deeper truth about how the bacterium may evolve and adapt to persist in different human populations."

According to the Health Protection Agency, the incidence of TB in the UK is increasing, but it still remains quite rare, with less than 7000 new cases a year. Cases in the UK are predominantly confined to the major cities and about 40% of all cases are in London. However, globally TB is a major problem: an estimated one third of the world's population – nearly two billion people – are infected. Ten million people a year develop the active disease worldwide, which kills three million each year.

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For further information please contact:

Craig Brierley
Media Officer
The Wellcome Trust
T: 020 7611 7329
E: c.brierley@wellcome.ac.uk

Notes to editors:

1. "A deletion defining a common Asian lineage of Mycobacterium tuberculosis associates with immune subversion" is scheduled to appear in Proceedings of the National Academy Sciences of the USA in October 2006.
Website: www.pnas.org 

2. The Wellcome Trust is the most diverse biomedical research charity in the world, spending about £450 million every year both in the UK and internationally to support and promote research that will improve the health of humans and animals. The Trust was established under the will of Sir Henry Wellcome, and is funded from a private endowment, which is managed with long-term stability and growth in mind.
Website: www.wellcome.ac.uk 

3. The Medical Research Council (MRC) is funded by the UK tax-payer. It aims to improve human health. The research it supports and the scientists it trains meet the needs of the health services, the pharmaceutical and other health-related industries and universities. The MRC has funded work which has led to some of the most significant discoveries and achievements in medicine in the UK.
Website: www.mrc.ac.uk 

4. Consistently rated in the top three UK university institutions, Imperial College London is a world leading science-based university whose reputation for excellence in teaching and research attracts students (11,000) and staff (6,000) of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and management and delivers practical solutions that enhance the quality of life and the environment - underpinned by a dynamic enterprise culture.
Website: www.imperial.ac.uk