| Summary: | <p>Abstract</p> <p>Background</p> <p>Enterohemorrhagic <it>Escherichia coli</it> (EHEC) colonizes the intestinal epithelium and causes attaching and effacing (A/E) lesions. Expression of virulence genes, particularly those from the locus of the enterocyte effacement (LEE) pathogenicity island is required for the formation of a type three secretion system, which induces A/E lesion formation. Like other horizontally acquired genetic elements, expression of the LEE is negatively regulated by H-NS. In the non-pathogenic <it>Escherichia coli</it> K-12 strain the stringent starvation protein A (SspA) inhibits accumulation of H-NS, and thereby allows de-repression of the H-NS regulon during the stationary phase of growth. However, the effect of SspA on the expression of H-NS-controlled virulence genes in EHEC is unknown.</p> <p>Results</p> <p>Here we assess the effect of SspA on virulence gene expression in EHEC. We show that transcription of virulence genes including those of the LEE is decreased in an <it>sspA</it> mutant, rendering the mutant strain defective in forming A/E lesions. A surface exposed pocket of SspA is functionally important for the regulation of the LEE and for the A/E phenotype. Increased expression of <it>ler</it> alleviates LEE expression in an <it>sspA</it> mutant, suggesting that the level of Ler in the mutant is insufficient to counteract H-NS-mediated repression. We demonstrate that the H-NS level is two-fold higher in an <it>sspA</it> mutant compared to wild type, and that the defects of the <it>sspA</it> mutant are suppressed by an <it>hns</it> null mutation, indicating that <it>hns</it> is epistatic to <it>sspA</it> in regulating H-NS repressed virulence genes.</p> <p>Conclusions</p> <p>SspA positively regulates the expression of EHEC virulence factors by restricting the intracellular level of H-NS. Since SspA is conserved in many bacterial pathogens containing horizontally acquired pathogenicity islands controlled by H-NS, our study suggests a common mechanism whereby SspA potentially regulates the expression of virulence genes in these pathogens.</p>
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