Abstract

Salmonella enterica serovar Typhimurium (Salmonella 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. We are currently using a primary human macrophage model system to dissect the roles of T3SS1 and T3SS2 in Salmonella-host cell interactions. We are also studying the expression of virulence genes in vitro.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI001111-09
Application #
9566714
Study Section
Project Start
Project End
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Budget End
Support Year
9
Fiscal Year
2017
Total Cost
Indirect Cost

  Institution

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Niaid Extramural Activities
Department
Type
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  Publications

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
Lathrop, Stephanie K; Cooper, Kendal G; Binder, Kelsey A et al. (2018) Salmonella Typhimurium Infection of Human Monocyte-Derived Macrophages. Curr Protoc Microbiol 50:e56
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
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
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; 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