Intestinal Epithelial Ecto-5 '-Nucleotidase Cd73 Regulates The Homeostasis Of Salmonella Typhimurium And Commensal Bacteria

Purine metabolism is central to the virulence of some enteric pathogens. CD73 is an ecto‐5′‐nucleotidase expressed abundantly on the apical surface of intestinal epithelial cells (IEC) and is rate limiting in the generation of extracellular adenosine. Previous work has shown that epithelial expression of CD73 facilitates transepithelial bacterial translocation and dissemination of Salmonella typhimurium. Based on these results, we hypothesized that apical expression of CD73 by IECs induces an invasive phenotype of Salmonella and the absence of CD73 expression results in a proliferative phenotype. Using mice with IEC‐specific deletion of CD73, we show that in a Salmonella colitis model, the abundance of Salmonella increases nearly 100‐fold within the contents of the cecum and colon of knockout animals in comparison to control animals. Furthermore, we show that adenosine inhibits growth of Salmonella and alters expression of some Salmonella pathogenicity islands in vitro . These data suggest that adenosine may directly impact Salmonella virulence and may occur through induction of an invasive rather than proliferative phenotype . The influence of CD73 on gut microbes does not appear to be specific to Salmonella . The microbiota of animals with IEC‐specific knockout of CD73 was analyzed by 16S rRNA pyrosequencing and differs dramatically from control animals. In conclusion, these findings show that expression of CD73 promotes virulence of the enteric pathogen Salmonella typhimurium through the production of luminal adenosine and is an important regulator of homeostasis of commensal bacteria.