Salmonella enterica serovar Typhimurium (S. Typhimurium) is a common cause of enterocolitis in humans and cattle but causes a systemic, typhoid-like, disease in susceptible mice. This facultative intracellular pathogen invades non-phagocytic cells, such as those found in the intestinal epithelium, and survives within a modified phagosome known as the Salmonella-containing vacuoles (SCV). Two type III secretion systems (T3SS), which translocate distinct cohorts of bacterial effector proteins into the host cell, are required for establishment of the intracellular replicative environment. Invasion is dependent on T3SS1 whereas T3SS2 is induced intracellularly and is associated with intracellular survival/replication and biogenesis of the SCV. A very important aspect of the host-pathogen interaction is the biogenesis of the SCV, from initial formation through to the ultimate release of bacteria. We have previously shown that SCV biogenesis involves sustained dynamic interactions with the endocytic pathway including late endosomes and lysosome. These studies were done using HeLa cells, which have been widely used in the field. However, one of our goals is to developing more physiologically relevant model systems. Therefore, we are using epithelial cell lines, such as MDCK cells (canine kidney) and C2Bbe1 (human colon), which can form polarized monolayers. We are focusing our efforts on the initial stages of SCV formation, including ruffle formation and SCV biogenesis.

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Knodler, Leigh A; Nair, Vinod; Steele-Mortimer, Olivia (2014) Quantitative assessment of cytosolic Salmonella in epithelial cells. PLoS One 9:e84681
Knodler, Leigh A; Crowley, Shauna M; Sham, Ho Pan et al. (2014) Noncanonical inflammasome activation of caspase-4/caspase-11 mediates epithelial defenses against enteric bacterial pathogens. Cell Host Microbe 16:249-56
Jolly, Carrie; Winfree, Seth; Hansen, Bryan et al. (2014) The Annexin A2/p11 complex is required for efficient invasion of Salmonella Typhimurium in epithelial cells. Cell Microbiol 16:64-77