The role of sugar acids in the regulation of virulence and intestinal colonization of attaching and effacing pathogens.

Enteric pathogens are capable of exploiting signals and nutrients derived from both the microbiota and the host to regulate their colonization and virulence programs. Here, we provide evidence that shows that attaching and effacing pathogens like Enterohemorrhagic Escherichia coli and C. rodentium utilize sugar acids to gain a foothold in the highly competitive environment that is the large intestine. We demonstrate that sugar acid utilization in the gut provides an early competitive advantage and subsequently contributes to the induction of virulence and perpetuation of this niche. We show that the sugar acid, galacturonic acid, inhibits the expression of virulence-related genes in an ExuR dependent manner. Sugar acid utilization is under the control of the ExuR transcriptional regulator. ExuR is capable of regulating EHEC virulence genes by interacting directly with the promoter region of the master regulator of a pathogenicity island known as the locus of enterocyte effacement (LEE). Our data suggest that sugar acid-mediated regulation of the LEE is a novel mechanism by which attaching and effacing pathogens can assure efficient colonization of the gut by ensuring niche establishment through the catabolism of galacturonic acid.