A novel anti-nutritional strategy that inhibits the newly identified Tyramine and D-glucuronic acid metabolic pathways in Salmonella
Primary author: Raquel Burin
Co-author: Devendra Shah
Faculty sponsor: Devendra Shah
Primary college/unit: College of Veterinary Medicine
Discovering the genetic mechanisms that Salmonella uses to elicit metabolic adaptations in the host is the key to find novel strategies to control Salmonella associated-disease. However, precise metabolites and the underlying metabolic pathways are relatively poorly understood. Previously we reported that deletion of genes involved in the catabolism of two micronutrients namely, tyramine (TYR) and d-glucuronic acid (DGA) resulted in decreased colonization and invasion of Salmonella in orally challenged mice. Given that TYR and DGA are found in the GI tract as byproducts of the gut microbial metabolism, it is likely that these micronutrients may serve as sources of energy to boost Salmonella growth and adaptation during the colonization process. The objectives of this study were to identify TYR and DGA catabolic pathways and to develop an innovative anti-nutritional approach to inhibit TYR and DGA nutritional adaptation of Salmonella. We conducted global transcriptome profiling of TYR and DGA-induced cultures of Salmonella. Next, we identified and employed anti-nutritional molecules to inhibit key enzymes committed to the first steps within the TYR and DGA catabolic pathways. We constructed novel TYR and DGA catabolic pathways in Salmonella and developed a novel strategy for the inhibition of these pathways thereby inhibiting the ability of Salmonella to utilize TYR and DGA as energy sources. We show that inhibition of metabolic enzymes and consequently the metabolism of TYR and DGA leads to nutrient adaptation defects in Salmonella. Further studies are ongoing to determine the utility of such anti-nutritional approach to control Salmonella in vivo.