Multi-omics reveal Salmonella-liberated dietary L-arabinose promotes expansion in superspreaders

Our understanding of specific metabolites that drive host-pathogen interactions in the guts of superspreader hosts is incomplete. In a mouse model of chronic, asymptomatic Salmonella enterica serovar Typhimurium (S. Tm) infection, we performed untargeted metabolomics on the feces of mice and found superspreader hosts possess distinct metabolic signatures compared to non-superspreaders, including differential levels of L-arabinose. RNA-seq on S. Tm in superspreader fecal samples showed increased expression of the L-arabinose catabolism pathway in vivo. By combining bacterial genetics and diet manipulation, we demonstrate that diet-derived L-arabinose provides S. Tm a competitive advantage in the gut. We show that expansion of S. Tm in the gut requires a previously uncharacterized alpha-N-arabinofuranosidase that can liberate L-arabinose from dietary polysaccharides. Ultimately, we demonstrate that pathogen-liberated L-arabinose from the diet provides a competitive advantage to S. Tm in vivo. These findings propose L-arabinose as a critical driver of S. Tm expansion in the guts of superspreader hosts.