The H-NS-like protein StpA represses the RpoS (sigma 38) regulon during exponential growth of Salmonella Typhimurium

StpA is a paralogue of the nucleoid-associated protein H-NS that is conserved in a range of enteric bacteria and had no known function in Salmonella Typhimurium. We show that 5% of the Salmonella genome is regulated by StpA, which contrasts with the situation in Escherichia coli where deletion of stpA only had minor effects on gene expression. The StpA-dependent genes of S. Typhimurium are a specific subset of the H-NS regulon that are predominantly under the positive control of sigma 38 (RpoS), CRP-cAMP and PhoP. Regulation by StpA varied with growth phase; StpA controlled sigma 38 levels at mid-exponential phase by preventing inappropriate activation of sigma 38 during rapid bacterial growth. In contrast, StpA only activated the CRP-cAMP regulon during late exponential phase. ChIP-chip analysis revealed that StpA binds to PhoP-dependent genes but not to most genes of the CRP-cAMP and sigma 38 regulons. In fact, StpA indirectly regulates sigma 38-dependent genes by enhancing sigma 38 turnover by repressing the anti-adaptor protein rssC. We discovered that StpA is essential for the dynamic regulation of sigma 38 in response to increased glucose levels. Our findings identify StpA as a novel growth phase-specific regulator that plays an important physiological role by linking sigma 38 levels to nutrient availability.