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. We are now focusing our efforts on the initial stages of SCV formation, with the goal of obtaining detailed proteomics data on the membrane ruffles and nascent phagosome. Host cell proteins enriched in these fractions are being followed up to establish their roles in the process.

Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2012
Total Cost
$544,726
Indirect Cost
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State
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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
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