Mycobacterium tuberculosis as viewed through a computer.

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 specific 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 identified 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 identified 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.