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Salmonella carriage in agricultural settings poses a major threat to national food safety, with 1.2 million people infected via contaminated food products each year in the United States. Prior work has demonstrated a role for Salmonella Pathogenicity Island 1 (SPI-1) in determining the outcome of Salmonella carriage. Our work shows that SPI-1 induction can be influenced by many environmental factors that are integrated at the level of the master regulator of gene expression: HilD. Here we aim to elucidate the mechanism by which HilD imposes phenotypic variation of SPI-1 induction by evaluating the HilD threshold concentration that triggers all-or-none activation of invasion gene expression. The long-term goal of this work is to characterize the bacterial mechanisms that determine proliferation and shedding of Salmonella in agricultural animals. In line with this goal, our central hypothesis is that SPI-1 expression is determined by HilD concentration, and that compounds that inhibit HilD expression or stability can prevent Salmonella pathogenicity.
Salmonella carriage in agricultural animals poses a major concern, as changes in the host environment can trigger rapid bacterial proliferation and shedding, thereby facilitating transmission. Prior work has demonstrated a role for Salmonella Pathogenicity Island 1 (SPI-1) in determining the outcome of such subclinical infections, and shows that SPI-1 induction is regulated by the transcriptional regulator HilD, which induces SPI-1 expression as an all-or-none event in individual bacteria. Here, we aim to elucidate the mechanism by which HilD imposes this phenotypic variance and thereby influences transmission of Salmonella. Our central hypothesis is that SPI-1 expression is a stable phenotype determined by HilD concentration, and that compounds inhibiting HilD can prevent Salmonella pathogenicity.