Characterization of two novel regulatory genes affecting Salmonella invasion gene expression

A Salmonella typhimurium chromosomal deletion removing approximate to 19 kb of DNA at centisome 65 reduces invasion of cultured epithelial cells as we ll as the expression of lacZY operon fusions to several genes required for the invasive phenotype. As the deleted region contains no genes previously known to affect Salmonella invasion, we investigated the roles of individua l genes in the deleted region using a combination of cloning, complementati on and directed mutation. We find that the deletion includes two unrelated regulatory genes. One is the Salmonella homologue of Escherichia coli barA (airS), which encodes a member of the multistep phosphorelay subgroup of tw o-component sensor kinases. The action of BarA is coupled to that of SirA, a member of the phosphorylated response regulator family of proteins, and i ncludes both HilA-dependent and HilA-independent components. The other regu latory gene removed by the deletion is the Salmonella homologue of E. coli csrB, which specifies a regulatory RNA implicated in controlling specific m essage turnover in E. coli. These results identify a protein that is likely to play a key role in the environmental control of Salmonella invasion gen e expression, and they also suggest that transcriptional control of invasio n genes could be subject to refinement at the level of message turnover.