Project Details
Description
Project Summary
Salmonellosis is one of the most significant food-borne diseases affecting humans and agriculture. Salmonella
enterica induces inflammation of the host intestinal tract, which disrupts the normal microbiota. Salmonella
then thrives on the nutrients that are not consumed by the microbiota. Salmonella nutrient sources include 1,2-
propanediol, which is a product of the microbiota; ethanolamine, which is derived from damaged cells;
glucarate and galactarate which are derived from Nos2-mediated oxidation of glucose and galactose; and
fructose-asparagine (F-Asn) which is derived from the diet. The F-Asn utilization system provides an
interesting therapeutic target as inhibition of the FraB enzyme intoxicates the bacterium with a metabolic
intermediate. Our primary objectives are to use a systems-level approach to identify the major nutrient sources
utilized by Salmonella over time in the inflamed gut and to identify the microbes that compete for those
nutrients. We hypothesize that some of these nutrient acquisition systems will provide therapeutic targets for
Salmonella and potentially other Enterobacteriaceae, including the carbapenem-resistant Enterobacteriaceae
(CRE) that are classified as an “urgent” threat by the CDC report, “Antibiotic resistance threats in the United
States”. In other cases, we hypothesize that the competing microbes could be utilized as probiotics or the
nutrients utilized could be utilized as prebiotics. We propose to fulfill our objectives and test our hypotheses
with the following two aims: 1) Identify the chemical and biological indicators of Salmonella-mediated
inflammation over time; 2) characterize metabolic exchanges between Salmonella and its competitors in the
gut. The fulfillment of these aims will greatly expand our understanding of the microbial ecology of
salmonellosis and may be broadly relevant to other pathogens or related inflammatory disorders.
Status | Finished |
---|---|
Effective start/end date | 09/24/18 → 08/31/23 |
Funding
- National Institute of Allergy and Infectious Diseases: $705,973.00
- National Institute of Allergy and Infectious Diseases: $705,973.00
- National Institute of Allergy and Infectious Diseases: $705,973.00
- National Institute of Allergy and Infectious Diseases: $719,973.00
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