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.
|Sridhar, Sushmita; Steele-Mortimer, Olivia (2016) Inherent Variability of Growth Media Impacts the Ability of Salmonella Typhimurium to Interact with Host Cells. PLoS One 11:e0157043|
|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|
|Spinner, Justin L; Winfree, Seth; Starr, Tregei et al. (2014) Yersinia pestis survival and replication within human neutrophil phagosomes and uptake of infected neutrophils by macrophages. J Leukoc Biol 95:389-98|
|Laughlin, Richard C; Knodler, Leigh A; Barhoumi, Roula et al. (2014) Spatial segregation of virulence gene expression during acute enteric infection with Salmonella enterica serovar Typhimurium. MBio 5:e00946-13|
|Cooper, Kendal G; Winfree, Seth; Malik-Kale, Preeti et al. (2011) Activation of Akt by the bacterial inositol phosphatase, SopB, is wortmannin insensitive. PLoS One 6:e22260|
|Knodler, Leigh A; Ibarra, J Antonio; Pérez-Rueda, Ernesto et al. (2011) Coiled-coil domains enhance the membrane association of Salmonella type III effectors. Cell Microbiol 13:1497-517|
|Knodler, Leigh A; Winfree, Seth; Drecktrah, Dan et al. (2009) Ubiquitination of the bacterial inositol phosphatase, SopB, regulates its biological activity at the plasma membrane. Cell Microbiol 11:1652-70|