Mycobacterium tuberculosis as viewed through a computer.pdfVIP

Opinion TRENDS in Microbiology Vol.13 No.5 May 2005 Mycobacterium tuberculosis as viewed through a computer Denise Kirschner and Simeone Marino Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-0260, USA Mathematical models are emerging as important tools in the study of microbiology. As an illustrative example, we present results from several models each generated to study the interaction of Mycobacterium tuberculosis and the immune system. Different mathematical models were formulated on the basis of assumptions regarding system–component interactions, enabling us to explore speci?c aspects at diverse biological scales (e.g. intracellular, cell–cell interactions, and cell population dynamics). In addition, we were able to examine both temporal and spatial aspects. At each scale, there were consistent themes that emerged as determinative in infection outcome. Factors we identi?ed include both host and microbial characteristics. The use of the models lies in generating hypotheses that can then be tested experimentally. Here, we outline the primary host and bacterial factors that we have identi?ed as key mechanisms that contribute to the success of M. tuberculosis as a human pathogen. Our goal is to stimulate experimentation and foster collaborations between theoretical and experimental scientists. Introduction Mycobacterium tuberculosis is one of the oldest human pathogens; evidence of tubercles has been found even in Egyptian mummies. The fantastic success of this organism is highlighted by the fact that one-third of the world is infected. Given its long association with humans, one might expect that the study of this pathogen would have revealed a range of virulence factors. Without becoming trapped in a cycle of de?nitions regarding virulence, it is clear that standard notions do not apply for M. tuberculosis. This poses an interesting conundrum for microbiologists; namely, how can arguably the world’s most succ