Abstract
BackgroundSalmonella enterica serovar Typhimurium is a common food-borne pathogen. S. enterica uses a type III secretion system encoded within Salmonella pathogenicity island 1 (SPI-1) to invade intestinal epithelial cells. A complex network of interacting transcription factors regulates SPI-1 gene expression. In addition, SPI-1 gene expression is coupled to flagellar gene expression. Both SPI-1 and flagellar gene expression are bistable, with co-existing populations of cells expressing and not expressing these genes. Previous work demonstrated that nutrients could be used to tune the fraction of cells expressing the flagellar genes. In the present study, we tested whether nutrients could also tune the fraction of cells expressing the SPI-1 genes through transcriptional crosstalk with the flagellar genes.ResultsNutrients alone were not found to induce SPI-1 gene expression. However, when the cells were also grown in the presence of acetate, the concentration of nutrients in the growth medium was able to tune the fraction of cells expressing the SPI-1 genes. During growth in nutrient-poor medium, acetate alone was unable to induce SPI-1 gene expression. These results demonstrate that acetate and nutrients synergistically activate SPI-1 gene expression. The response to acetate was governed by the BarA/SirA two-component system and the response to nutrients was governed by transcriptional crosstalk with the flagella system, specifically through the action of the flagellar regulator FliZ.ConclusionsAcetate and nutrients are capable of synergistically activating SPI-1 gene expression. In addition, these signals were found to tune the fraction of cells expressing the SPI-1 genes. The governing mechanism involves transcriptional crosstalk with the flagellar gene network. Collectively, these results further our understanding of SPI-1 gene regulation and provide the basis for future studies investigating this complex regulatory mechanism.
Highlights
Salmonella enterica serovar Typhimurium is a common food-borne pathogen
We Synergistic activation of Salmonella pathogenicity island 1 (SPI-1) gene expression by acetate and yeast extract Previous work has shown that flagellar gene expression is bistable in S. enterica, and that the fraction of motile cells is determined by the nutrient concentration in the growth medium [30]
Because the expression of the SPI1 genes in S. enterica is coupled to the expression of the flagellar genes, we sought to determine whether nutrients would tune the expression of the SPI-1 genes
Summary
Salmonella enterica serovar Typhimurium is a common food-borne pathogen. S. enterica uses a type III secretion system encoded within Salmonella pathogenicity island 1 (SPI-1) to invade intestinal epithelial cells. We tested whether nutrients could tune the fraction of cells expressing the SPI-1 genes through transcriptional crosstalk with the flagellar genes. Salmonella enterica serovar Typhimurium is a common food-borne pathogen. HilA expression, in turn, is regulated by three transcription factors: HilC, HilD, and RtsA, which positively regulate their own expression and that of each other [5]. Among these three factors, HilD is the main regulator of HilA expression – many of the signals inducing SPI-1 gene expression do so by altering the expression or activity of HilD. HilC and RtsA, on the other hand, appear to amplify HilA expression [5, 6]
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