Enterohemorrhagic E. coli (EHEC) O157:H7 is a foodborne pathogen that causes hemorrhagic colitis and hemolytic-uremic syndrome. A spatiotemporal regulation of virulence genes is required by gut pathogens to colonize their ecological niche and cause disease. EHEC require the expression of a type III secretion system (T3SS) to attach the colonic epithelium and cause disease in humans. The T3SS encoding genes are regulated by intestinal metabolites including carbon and nitrogen sources.
Using gnotobiotic rats, we have shown that the expression level of T3SS encoding genes of the EHEC O157:H7 strain EDL933 is decreased in the cecal content of rats associated with the human gut microbiota compared to that in the germfree rat’s cecal content. The down-regulation of T3SS encoding genes is even more important when rats are mono-associated with Bacteroides thetaiotaomicron (Bt), a predominant gut symbiont. Using mass spectrometry, we measured the concentration of several compounds contributing to the colonization of the gut by EHEC in the cecal contents. We have found that Bt greatly enhances the cecal amount of sialic acid or N-acetylneuraminic acid (Neu5Ac). In a defined medium, Neu5Ac reduces the expression of T3SS encoding genes and the secretion of T3S secreted proteins. Mutagenesis analysis revealed that the repression depends of the assimilation of Neu5Ac by EDL933, suggesting the involvement of an intracellular signal leading to repression of virulence genes.
Neu5Ac is a nine-carbon keto sugar occupying the interface between the host and commensal or pathogenic microorganisms. Neu5Ac also are excellent sources of carbon, nitrogen, and precursors of cell wall biosynthesis. We have shown that catabolism of Neu5Ac participate in the regulation virulence genes. We are investigating the regulatory factors required for the inhibition of T3SS genes in response to Neu5Ac. These data provide clues for a better understanding of symbiont- and host-pathogen interactions.