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 found that efficient invasion of intestinal epithelial cells is facilitated by smooth swimming. A chemoreceptor, McpC, is co-expressed with T3SS1 which is required for efficient invasion. 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. We are now developing additional autolytic strains and environmental sensors that can provide information about specific sub populations of Salmonella in the mammalian gut. We are also looking at signaling pathways in infected epithelial cells to try to dissect the roles of specific bacterial effector proteins.