Salmonella enterica serovar Typhimurium is one of the most common causes of enterocolitis in humans. 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. Since the expression and function of these virulence factors is exquisitely dependent on the intracellular environment, we are focusing on developing appropriate in vitro systems to study their activities at the molecular level.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2012
Total Cost
$544,726
Indirect Cost
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State
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Starr, Tregei; Bauler, Timothy J; Malik-Kale, Preeti et al. (2018) The phorbol 12-myristate-13-acetate differentiation protocol is critical to the interaction of THP-1 macrophages with Salmonella Typhimurium. PLoS One 13:e0193601
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Lathrop, Stephanie K; Binder, Kelsey A; Starr, Tregei et al. (2015) Replication of Salmonella enterica Serovar Typhimurium in Human Monocyte-Derived Macrophages. Infect Immun 83:2661-71
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