Fis regulates transcriptional induction of RpoS in Salmonella enterica

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 serving rpoS in Salmonella enterica serovar 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. Afis mutant of S. enterica serovar Typhimurium showed a ninefold increase in expression from the major rpoS promoter (P-rpoS) during exponential growth, whereas expression during SP was unaffected. Increased transcription from P-rpos in the absence of Fis eliminated the transcriptional induction as cells enter SP. The mutant phenotype can be complemented by wild-type fis carried on a single-copy plasmid. Fis regulation of rpoS requires the presence of a Fis site positioned at -50 with respect to PIP, and this site is bound by Fis in vitro. A model is presented in which Fis binding to this site allows repression of rpoS specifically during exponential growth, thus mediating transcriptional regulation of rpoS.