The overall theme of our research centers on understanding how the pathogenic bacterium Mycobacterium tuberculosis (Mtb) exploits environmental cues to survive and grow in its host. What host environmental signals serve as cues for Mtb in determining its location in the host? How are these cues sensed and responded to? How do these responses enable Mtb to usurp or modify host processes to create a replicative niche for itself? In addition, we are interested in the basis and impact on infection outcome of the marked heterogeneity observed during Mtb infection, particularly with respect to environmental cues. We explore these questions using macrophage and murine infection models, and novel fluorescent reporter Mtb strains that allow mechanistic studies in vitro, and that facilitate studies of Mtb responses in vivo at the level of the single bacterium.