SsrB regulates genes outside SPI-2 to affect Salmonella Typhimurium lifestyle

Abstract

Salmonella enterica serovar Typhimurium is a gram-negative intracellular pathogen known to cause gastro-intestinal infections. The Salmonella Pathogenicity Islands (SPI) are key to its pathogenesis. SsrB, encoded on SPI-2, acts as a regulatory switch between the intracellular disease-causing state and the extracellular biofilm forming state of Salmonella Typhimurium. Studying the SsrB regulon can provide insights into the role of a horizontally acquired regulator in modulating gene expression of the native chromosome and in turn regulation key aspects of pathogenesis. Transcriptome data from two day old Salmonella Typhimurium biofilms of an ssrB null strain identified a repertoire of genes that were differentially expressed. A subgroup which were downregulated included Hfq (an RNA chaperone), dsrA (a sRNA) and DksA (a stringent response regulator). To establish how SsrB regulates these genes, binding of SsrB to their regulatory regions was examined by electrophoretic mobility assays. SsrB was found to bind all three regulatory regions. DksA and dsrA are known to be important for the Acid Tolerance Response (ATR) in Salmonella Typhimurium. When we examined the ATR of the ssrB null strain, we found it to have a reduced survival in pH 3.3 as compared to the wild-type. In order to identify the mechanism of SsrB-mediated regulation of ATR, dsrA and dksA null strains were generated. However, due to high variations within experiments, further work is necessary to investigate this mechanism.