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High throughput sequencing to reveal the causes and consequences of Mycobacterium tuberculosis genomic variation

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The evolution of tuberculosis

Mycobacterium tuberculosis has two faces: it can either cause acute or chronic disease. Using state-of-the-art sequencing methods, European researchers attributed this phenomenon to genomic diversity.

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Tuberculosis remains one of the leading causes of mortality worldwide, accounting for approximately two million deaths per year. Despite extensive research, the only means of decreasing disease risk is the BCG vaccine, which confers protection for a limited time only. M. tuberculosis is genetically diverse and different bacterial lineages are associated with varied clinical and epidemiological manifestations of the disease. Understanding the determinants of bacterial evolution and genomic diversity could have important implications for the design of future therapeutic interventions. The EU-funded MTB VARIATION project set out to investigate the evolution of M. tuberculosis and its characteristics. In this context, scientists sequenced the genome of nearly 260 different genetic bacterial isolates collected from various parts of the world. Comparative genomic analysis unravelled more than thirty thousand single nucleotide polymorphisms of putative therapeutic potential. Evolutionary analyses of the different bacterial lineages revealed a perfect correlation among bacterial and human population migration and dynamics. Also, the success of the human population during the Neolithic period seemed to support the success of tuberculosis spread and its global domination. Interestingly, researchers found that M. tuberculosis also managed to survive in small groups of hunt-gatherers probably through domination of less virulent strains. When host numbers were not a limitation, M. tuberculosis probably switched to more virulent strains. As a result, the identification of the genetic determinants of this transition may provide the answer to the eradication of tuberculosis. Project results provide unprecedented insight into the genomic diversity and evolution of M. tuberculosis. Future studies on selective and non-selective environmental pressure could be exploited to further comprehend the virulence and epidemiology of this serious pathogen.


Mycobacterium tuberculosis, sequencing, genomic diversity, epidemiological, evolution, single nucleotide polymorphism

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