Fis Regulates Transcriptional Induction of RpoS inSalmonella enterica

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Abstract
The sigma factor RpoS is known to regulate at least 60 genes in response to environmental sources of stress or during growth to stationary phase (SP). Accumulation of RpoS relies on integration of multiple genetic controls, including regulation at the levels of transcription, translation, protein stability, and protein activity. Growth to SP in rich medium results in a 30-fold induction of RpoS, although the mechanism of this regulation is not understood. We characterized the activity of promoters servingrpoSinSalmonella entericaserovar Typhimurium and report that regulation of transcription during growth into SP depends on Fis, a DNA-binding protein whose abundance is high during exponential growth and very low in SP. Afismutant ofS. entericaserovar Typhimurium showed a ninefold increase in expression from the majorrpoSpromoter (PrpoS) during exponential growth, whereas expression during SP was unaffected. Increased transcription from PrpoSin the absence of Fis eliminated the transcriptional induction as cells enter SP. The mutant phenotype can be complemented by wild-typefiscarried on a single-copy plasmid. Fis regulation ofrpoSrequires the presence of a Fis site positioned at −50 with respect to PrpoS, and this site is bound by Fis in vitro. A model is presented in which Fis binding to this site allows repression ofrpoSspecifically during exponential growth, thus mediating transcriptional regulation ofrpoS.