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. Recently we have been investigating the relative importance of vacuolar versus cytosolic replication in epithelial cells. In approximately 5-20% of infected cells S. Typhimurium escape from the vacuole and survive and replicate in the cytosol. We have found that these cytosolic bacteria trigger a non canonical caspase 4/11 inflammasome response that is important for antimicrobial defense in the intestinal epithelium. Currently we are completing a study showing that at later time points the T3SS1 is functionally active in the cytosolic bacteria whereas the T3SS2 is functionally active only in the vacuolar bacteria.

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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
Finn, Ciaran E; Chong, Audrey; Cooper, Kendal G et al. (2017) A second wave of Salmonella T3SS1 activity prolongs the lifespan of infected epithelial cells. PLoS Pathog 13:e1006354
Cooper, Kendal G; Chong, Audrey; Starr, Tregei et al. (2017) Predictable, Tunable Protein Production in Salmonella for Studying Host-Pathogen Interactions. Front Cell Infect Microbiol 7:475
Wrande, Marie; Andrews-Polymenis, Helene; Twedt, Donna J et al. (2016) Genetic Determinants of Salmonella enterica Serovar Typhimurium Proliferation in the Cytosol of Epithelial Cells. Infect Immun 84:3517-3526
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
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 16:249-256
Knodler, Leigh A; Nair, Vinod; Steele-Mortimer, Olivia (2014) Quantitative assessment of cytosolic Salmonella in epithelial cells. PLoS One 9:e84681
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
Steele-Mortimer, Olivia; Subtil, Agathe (2014) Editorial overview: Host-microbe interactions: bacteria. War and peace: the fragile equilibrium between bacteria and host. Curr Opin Microbiol 17:v-vii
Malik-Kale, Preeti; Winfree, Seth; Steele-Mortimer, Olivia (2012) The bimodal lifestyle of intracellular Salmonella in epithelial cells: replication in the cytosol obscures defects in vacuolar replication. PLoS One 7:e38732

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