Salmonella-Mediated Inflammation Eliminates Competitors for Fructose-Asparagine in the Gut

Abstract

<i>Salmonella enterica</i> elicits intestinal inflammation to gain access to nutrients. One of these nutrients is fructose-asparagine (F-Asn). The availability of F-Asn to <i>Salmonella</i> during infection is dependent upon <i>Salmonella</i> pathogenicity islands 1 and 2, which in turn are required to provoke inflammation. Here, we determined that F-Asn is present in mouse chow at approximately 400 pmol/mg (dry weight). F-Asn is also present in the intestinal tract of germfree mice at 2,700 pmol/mg (dry weight) and in the intestinal tract of conventional mice at 9 to 28 pmol/mg. These findings suggest that the mouse intestinal microbiota consumes F-Asn. We utilized heavy-labeled precursors of F-Asn to monitor its formation in the intestine, in the presence or absence of inflammation, and none was observed. Finally, we determined that some members of the class <i>Clostridia</i> encode F-Asn utilization pathways and that they are eliminated from highly inflamed <i>Salmonella</i>-infected mice. Collectively, our studies identify the source of F-Asn as the diet and that <i>Salmonella</i>-mediated inflammation is required to eliminate competitors and allow the pathogen nearly exclusive access to this nutrient.