Salmonella enterica Coordination of Virulence Gene Expression and Carbon Metabolism during Infection

Salmonella enterica, which consists of zoonotic, rod-shaped, Gram-negative bacteria, is the cause of about 78 million cases of foodborne illness each year and is the leading cause of death by bacterial foodborne illnesses in the world. The category of foodborne illnesses itself is responsible for about $152 billion of annual economic losses. When Salmonella enterica serovar Typhimurium infects its host, the CsrA and BarA-SirA system regulates the expression of metabolic and virulence genes. Our goal is to determine the activity of the CsrA and BarA-SirA system during infection and how this activity coordinates carbon metabolism and the expression of virulence genes. We hypothesize that CsrA activity is low during intestinal infection and high during systemic infection. To test this hypothesis, genes of interest were cloned into translational fusion vectors containing a mCherry fluorescent reporter. These vectors were inserted at flippase recognition target (FRT) sites in the Salmonella chromosome of wild type, sirA mutant, and csrA mutant strains. During growth in the presence or absence of glucose and under conditions that induce Salmonella Pathogenicity Islands 1 and 2, these strains were assayed in vitro to replicate the intestinal and systemic environments in which these pathogenicity islands are expressed so that in the future, the results can be further analyzed in vivo. Preliminary findings show that CsrA activity is present in vitro based on the regulation of the genes of interest by CsrA. The outcomes of this study will not only enhance our understanding of the interaction between host and pathogen, but they will also be a stepping stone to the development of therapeutics against an illness that affects so many around the world.A five-year embargo was granted for this item.Academic Major: Microbiolog