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Salmonella enterica  serovar Typhimurium ( Salmonella ) is one of the most significant food-borne pathogens affecting both humans and agriculture. We have determined that  Salmonella  encodes an uptake and utilization pathway specific for a novel nutrient, fructose-asparagine (F-Asn), which is essential for  Salmonella  fitness in the inflamed intestine (modeled using germ-free, streptomycin-treated, ex-germ-free with human microbiota, and IL10 −/−  mice). The locus encoding F-Asn utilization,  fra , provides an advantage only if  Salmonella  can initiate inflammation and use tetrathionate as a terminal electron acceptor for anaerobic respiration (the  fra  phenotype is lost in  Salmonella  SPI1 −  SPI2 −  or  ttrA  mutants, respectively). The severe fitness defect of a  Salmonella fra  mutant suggests that F-Asn is the primary nutrient utilized by  Salmonella  in the inflamed intestine and that this system provides a valuable target for novel therapies.

Fructose-Asparagine Is a Primary Nutrient during Growth of Salmonella in the Inflamed Intestine