Invasion and intracellular replication of Salmonella Typhimurium in epithelial cells

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

Salmonella enterica serovar Typhimurium (Salmonella 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, particularly intestinal epithelial cells. We have previously shown that efficient invasion of intestinal epithelial cells is facilitated by smooth swimming mediated by the chemoreceptor, McpC. We are now studying the role of a second chemoreceptor, McpA, that is co-expressed with McpC. Intracellular replication occurs within the SCV and within the cytosol, bacterial growth rates and transcriptional status within these two intracellular niches are quite different. In particular, the T3SS1 is functionally active in the cytosolic bacteria whereas the T3SS2 is functionally active in the vacuolar bacteria. Thus, each of the T3SS systems are functional in the intracellular environment albeit in different niches. Previously we have developed an environmental autolytic strain, that lysis in the cytosol of mammalian cells, to study the role of the cytosolic population. Using bioengineered Salmonella to either report their intracellular localization (fluorescence protein expression) or to lyse in specific intracellular compartments (lytic gene expression) we are studying how Salmonella intersect signaling pathways in infected epithelial cells and how this impacts survival of the infected host cell or bystanders. Oral infection of naturally resistant mice (e.g. 129X1/SvJ) with Salmonella Typhimurium leads to chronic infection with a small percentage of animals shedding high levels of Salmonella in their feces (super shedders). We are using this model to investigate the factors involved in shedding and persistence and the role played by intestinal epithelial cells.