Dissertation
AN ANTI-NUTRITIONAL STRATEGY THAT INHIBITS THE NEWLY IDENTIFIED TYRAMINE AND D-GLUCURONIC ACID METABOLIC NETWORKS IN NON-TYPHOIDAL SALMONELLA
Doctor of Philosophy (PhD), Washington State University
01/2020
Handle:
https://hdl.handle.net/2376/112198
Abstract
The access to host nutrients in the gastrointestinal (GI) tract and other tissues of the host is fundamental for Salmonella growth, virulence and disease progression. To meet energy demands within such hostile environment and to overcome nutrient competition by the host microbiota, Salmonella has evolved various metabolic adaptations to preferentially derive energy from the byproducts of the host gut microbial metabolism. Discovering the genetic mechanisms that Salmonella uses to elicit metabolic adaptations is the key to find strategies to control Salmonella associated-disease. However, metabolic preferences of Salmonella are relatively poorly understood. Previously we reported that deletion of genes involved in metabolism 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 and other host tissues as byproducts of the 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 metabolic pathways and to develop an innovative anti-nutritional approach to inhibit TYR and DGA nutritional adaptation of Salmonella. We employed RNA-seq to obtain transcriptomes of Salmonella exposed to TYR and DGA. Next, we developed an anti-nutritional strategy wherein the key enzymes committed to the first steps within the TYR and DGA metabolic pathways are inhibited. The RNA-seq allowed us to construct novel TYR and DGA metabolic pathways in Salmonella and the inhibition of these pathways led to inability of Salmonella to utilize TYR and DGA as sources of energy. This study highlights the new paradigm wherein inhibition of metabolic enzymes and consequently the metabolism of TYR and DGA leads to nutrient adaptation defects in Salmonella. Further studies are warranted to determine the utility of such anti-nutritional approach to control Salmonella in vivo.
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Details
- Title
- AN ANTI-NUTRITIONAL STRATEGY THAT INHIBITS THE NEWLY IDENTIFIED TYRAMINE AND D-GLUCURONIC ACID METABOLIC NETWORKS IN NON-TYPHOIDAL SALMONELLA
- Creators
- Raquel Cristina Konrad Burin
- Contributors
- Devendra H. Shah (Advisor)Leigh A. Knodler (Committee Member)William B. Davis (Committee Member)Santanu Bose (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Veterinary Medicine, College of
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 123
- Identifiers
- 99900581409601842
- Language
- English
- Resource Type
- Dissertation