Gene Regulation of Tartrate Metabolism in Salmonella typhimurium

Salmonella Typhimurium (S. Tm) triggers an inflammatory response in the gut that favors the outgrowth of the pathogen over the resident microbiota. Early in S. Tm infection, oxidation of simple sugars by reactive nitrogen and oxygen species gives rise to L- and D-tartrate, which support fumarate reduction in a branched TCA cycle. At later time points, a neutrophil-derived oxidative burst facilitates an oxidative central metabolism in S. Tm and represses tartrate utilization. We sought to understand how Salmonella coordinates its gene expression of carbon and energy sources as it experiences transient nutrient niches to facilitate a branched TCA cycle during early events in infection versus at later time points when an oxidative central metabolism is supported. Specifically, we investigated the mechanism of gene regulation regarding L and D-tartrate metabolism, a previously unexplored area of Salmonella metabolism. Bacterial genetics and traditional biochemical methods such as -galactosidase transcriptional reporters and Electrophoretic Mobility Shift Assays (EMSA) allowed us to create a specific model for the gene regulation of L-tartrate metabolism. Furthermore, in vivo studies using murine models of colitis suggested that gene regulation for L-tartrate metabolism in Salmonella is required for optimal fitness during infection. The gene regulation for D-tartrate metabolism was additionally investigated. The use of in vitro gene expression measurements and bacterial genetics revealed a complex regulatory mechanism that requires further study. In conclusion, we used tartrate metabolism as an example to explain how Salmonella seeks to benefit from carbon and energy sources as it experiences transient nutrient niches during intestinal inflammation.

Author dc:creator

• Rojas, Vivian Kimberly

Contributors dc:contributor

• Hendrixson, David R.
• Schoggins, John W.
• Greenberg, David
• Forsberg, Kevin J.
• Winter, Sebastian E.

• Bacterial Proteins
• Gene Expression Regulation, Bacterial
• Salmonella Infections
• Salmonella typhimurium
• Tartrates

Language dc:language

en

Identifier

1596185289

OAI identifier oai:identifier

oai:utswmed-ir.tdl.org:2152.5/10810