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Genetic Analysis of the host-pathogen interaction in tuberculosis

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Delicate balance between tuberculosis and humans

Despite the early promise of vaccines and antibiotics, tuberculosis is still spreading. A massive European study has begun to extend databases with bio-information on the TB mycobacterium responsible and genetic profiles of patients.

Health

One third of the world's population is thought to be infected with mycobacterium tuberculosis (TB) which causes the disease with the same name. Although most infections remain latent, one in ten develops an active infection. Treatment of TB poses many problems. The existence of many strains, including antibiotic-resistant types, is one of the most important. Prevention relies on screening and immunisation with the Bacillus Calmette-Guerin (BCG) which is not 100\;% effective. Varying protection is gained from the BCG mainly because of genetic variability of both the bacterium and the population. Add to this the opportunistic nature of the disease, which takes advantage of the reduced immunity status of HIV sufferers, and two million deaths per year globally come as no surprise. The EU-funded project TB-EURO-GEN is finding out why so many in a population can remain disease-free even though infected. The aim is to understand the relationship between the mycobacterium and the human host, and the genetic reasons for being susceptible to developing active TB. This they hope will lead to the discovery of genes for resistance to the disease. To obtain meaningful data requires large trials. The TB-EURO-GEN team have already successfully recruited 5\;000 people for a control group and 3\;700 TB patients. The aim is to extend the number of patients to 5\;000 and to extract their DNA as well as the infecting TB DNA. Human DNA has also been collected from Ghana, another country with a high incidence of TB. The DNA is being analysed to isolate genes that predispose the patient to development of active TB. State-of-the-art genetic techniques are being used to accumulate the vast amount of data. Through collaboration with the Sanger Institute in the UK, 200 M. tuberculosis strains have been analysed using a next-generation whole genome sequencing technique. Spolygotyping, a rapid yet accurate technique to analyse the genome, has been used on Euro-American and East Asian families to define the genetic ancestry of TB. The matching of a statistically powerful number of samples from a multi-ethnic base is seen as the key to combating the growing problem of the disease. This promises to open up new possibilities for the development of vaccines and new targets for TB prevention.

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