A molecular biology approach to tuberculosis

  1. Michel Tibayrenc*
  1. Unité Mixte de Recherche, Institut de Recherche pour le Développement/Centre National de la Recherche Scientifique 2724 “Genetics and Evolution of Infectious Diseases,” BP 64501, 34394 Montpellier Cedex 5, France

There is little doubt that infectious diseases are the major challenge of medicine at the opening of this new century (1). They are still by far the major population control factor of our species. At the very least, this peril of emerging and reemerging infectious diseases (2) has the beneficial side effect of boosting basic research. It is indeed a paradox that, for example, the basic biology of Mycobacterium tuberculosis, the causative agent of a major human disease, is far less well known than that of Escherichia coli, potentially because tuberculosis was more or less effectively controlled in the north. Facing the threat of tuberculosis epidemics throughout the world, scientists are currently erasing the somewhat artificial border between basic and applied research and are generating data that have both a strong added value in terms of basic science and an immediate usefulness for epidemiology and medicine. The two companion papers by Tsolaki et al. (3) and Hirsh et al. (4) in this issue of PNAS are perfect examples of this new scientific school, as well as of the opportunities offered by the progress of modern biotechnology when they are wisely used.

Like many organisms, the whole genome of M. tuberculosis has now been entirely sequenced (5). In itself, this is a major technological achievement that carried with it a great deal of raw material and crude data. The analysis of this bacterium's genome sequence has itself led to informative hypotheses on its biology (6). However, because only one reference strain (H37Rv) was originally sequenced (5), information on the species' genetic variability was lacking. Using this sequence and the powerful technology of microarrays, Tsolaki, Hirsh, and colleagues (3, 4) built a highly resolvent tool of comparative genomics to explore the genetic diversity of 100 M. tuberculosis isolates from …

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