Catabolite repression of the SirA regulatory cascade in Salmonella enterica.
Orthologs of the Salmonella BarA/SirA two-component system are required for virulence, motility, secondary metabolism and stress survival throughout the gamma-proteobacteria. BarA is a sensor kinase that responds to an unknown signal by phosphorylating the response regulator SirA. SirA increases the expression of genes within Salmonella pathogenicity island 1 (SPI1) that encode a type III secretion system (TTSS-1). SirA does this by directly activating the hilA and hilC regulatory genes encoded within SPI1. SirA also directly activates the csrB regulatory RNA gene. This RNA antagonizes the activity of the post-transcriptional regulatory protein CsrA that binds the mRNA of its targets to regulate SPI1, motility and secondary metabolism. A second regulatory RNA, csrC, is also strongly regulated by SirA, although gel mobility shift assays do not demonstrate a direct interaction. Additionally, we have determined that the sirA gene is activated by crp and cya. The effects of crp and cya were also observed on the downstream members of the SirA regulon, hilA, sopB, csrB, and csrC. However, gel mobility shift experiments and DNA sequence analysis suggest that the regulation of sirA by CRP is probably indirect. Although SirA does not regulate csrA, this gene was also under crp/cya control. Supplementation of a rich medium with phosphate diminished the catabolite control of the csr portion but not the virulence portion of the SirA regulon.
Teplitski
Max
M
Department of Soil and Water Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611-0290, USA. maxtep@ufl.edu
Goodier
Robert I
RI
Ahmer
Brian M M
BM
D000222:Adaptation, Physiological; D000262:Adenylyl Cyclases / Q000378:metabolism*; D019677:Artificial Gene Fusion; D001426:Bacterial Proteins / Q000096:biosynthesis*; D002373:Cyclic AMP Receptor Protein / Q000502:physiology*; D004269:DNA, Bacterial / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D015964:Gene Expression Regulation, Bacterial; D011485:Protein Binding; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000096:biosynthesis*; D037521:Virulence Factors / Q000096:biosynthesis; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D001426:Bacterial Proteins; D002373:Cyclic AMP Receptor Protein; D004269:DNA, Bacterial; C104847:SirA protein, Salmonella; D015534:Trans-Activators; D037521:Virulence Factors; D001616:beta-Galactosidase; D000262:Adenylyl Cyclases