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Researchers have uncovered genetic secrets of the tuberculosis (TB) bacterium that may be contributing to the surge in multidrug resistance to the disease.

The study — one of the first to investigate the global diversity of TB bacteria — has found that they are far more genetically diverse than was assumed.

The researchers examined genes in 99 strains of Mycobacterium tuberculosis, which causes TB. They also looked at nine animal-specific strains.

To their surprise they found greater genetic diversity between human TB strains than between animal-adapted strains, contradicting the previously held belief that all human TB strains are essentially the same.

"We found that TB is not clonal — all the same — as was assumed," says Sebastien Gagneux, co-author, formerly of the US-based Institute of Systems Biology and now at the National Institute for Medical Research, United Kingdom.

The team also found that the bacteria undergo low rates of genetic selection. They accumulate mutations in their DNA by a process known as genetic drift and there are few selection pressures around to curb these mutations.

Because of this, mutations that confer drug resistance are not removed from the gene pool and persist in populations.

Normally, gene mutations that confer drug resistance are actually damaging to bacteria because they are acquired at the cost of weakening some other aspect of its machinery. This keeps drug resistance in check. But this does not seem to be the case with TB.

The researchers, whose work was published in PLoS Biology this month (16 December), found that human TB falls into two distinct groups: 'ancient' strains found only in West Africa and along the rim of the Indian Ocean, and 'modern' lineages that dominate Europe, the Americas, East Asia, East Africa and India.

The scientists found correlations between genetic and geographical distances, suggesting that ancient human land migration routes out of Africa carried TB north into Europe and east around the Indian Ocean, but the modern strains have migrated back to Africa via sea routes.

"It is possible that ancient strains have been forced out by modern ones, for instance in the Caribbean, where only modern strains are present although ancient TB would have arrived there due to the slave trade," Gagneux told SciDev.Net.

Because of this — and today's global travel — the designers of TB control programmes should take geographic strain diversity into account, say the researchers.

Link to full article in PLoS Biology


PLoS Biology doi 10.1371/journal.pbio.0060311 (2008)

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