Diet-derived galacturonic-acid regulates virulence and intestinal colonization in enterohemorrhagic E. coli and Citrobacter rodentium.

Enteric pathogens sense the complex chemistry within the gastrointestinal (GI) tract to efficiently compete with the resident microbiota and establish a colonization niche. Here we show that enterohemorrhagic E. coli (EHEC), and its surrogate murine infection model Citrobacter rodentium, sense galacturonic-acid to initiate a multi-layered program towards successful mammalian infection. Galacturonic-acid utilization as a carbon source aids the initial pathogen expansion. The main source of galacturonic-acid is dietary pectin, which is broken into galacturonic-acid by the prominent member of the microbiota, Bacteroides thetaiotamicron (Bt). This regulation occurs through the ExuR transcription factor. However, galacturonic-acid is also sensed as a signal through ExuR to modulate the expression of the genes encoding a molecular syringe known as a type three secretion system (T3SS) leading to infectious colitis and inflammation. Galacturonic-acid moonlights as a nutrient and a signal directing the exquisite microbiota-pathogen relationships within the GI tract. Importantly, this work highlights that differential dietary sugar availability impacts the relationship between the microbiota and enteric pathogens, as well as disease outcomes.