A post-transcriptional link between Salmonella metabolism and virulence

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This project aims to explore a novel type of post-transcriptional integration of sugar metabolism and virulence factor expression in the model pathogen, Salmonella enterica serovar Typhimurium. We will investigate the bifunctional SgrS RNA which has recently been described as a phosphosugar stress-induced repressor of ptsG mRNA encoding the primary glucose transporter IICBGlc in nonpathogenic E. coli. Our preliminary work in Salmonella has not only confirmed the regulation of ptsG but also discovered new targets of SgrS. These include a repression of sopD encoding a horizontally acquired protein that is translocated into host cells by the Salmonella type 3 secretion apparatus, and an activation of yigL whose gene product is a putative hydrolase with high affinity for glucose-6-phosphate. Given that glucose is the major carbon source of intracellular Salmonella, we speculate that SgrS might constitute a novel post-transcriptional node that helps coordinate metabolism and virulence factor expression. Exploiting the expertise available in SPP1316, we will establish relevant growth conditions and cell types study the activity of SgrS during the course of infection. Transcriptomics and metabolic profiling will be used to determine the physiological consequences of SgrS-mediated regulation of its target genes for carbon flux and utilization to reconstruct a network of genetic control by SgrS upon invasion and during intracellular replication.