Salmonella enterica serovar Typhimurium is a common cause of enterocolitis in humans and cattle but causes a systemic, typhoid-like, disease in susceptible mice. Pathogenesis of this facultative intracellular pathogen is dependent on the ability to invade non-phagocytic cells, such as those found in the intestinal epithelium. Invasion is dependent on a type III secretion system (T3SS1), which is used to translocate a set of bacterial effector proteins into the host cell. Following internalization intracellular Salmonella survive and replicate within a modified phagosome, the Salmonella-containing vacuole (SCV). A second type III system (T3SS2) is induced intracellularly and is associated with intracellular survival/replication and biogenesis of the SCV. To understand Salmonella pathogenesis we must dissect the roles of the individual T3SS1 and T3SS2 effector proteins as well as the mechanisms that control their expression and activity inside host cells. The T3SS1 effector SopB/SigD, is an inositol phosphatase that is involved in bacterial uptake but also induces the activation of mammalian serine threonine kinase Akt/PKB and can prevent the onset of apoptosis in epithelial cells. Efficient translocation of SopB is dependent on binding to its cognate chaperone SigE/PipC. We have now characterized the SigE residues involved in formation and stabilization of the heteromeric complex.[unreadable] Another important aspect of the host-pathogen interaction is the biogenesis of the SCV. A widely held belief, based on work from several labs, is that Salmonella prevent SCV-lysosome fusion and that this is an important requisite for intracellular survival and replication. We have now shown that, contrary to this dogma, SCV biogenesis involves sustained dynamic interactions with the endocytic pathway including late endosomes and lysosome.