Virulence factors enhance Citrobacter rodentium expansion through aerobic respiration

Citrobacter rodentium uses a type III secretion system (T3SS) to induce colonie crypt hyperplasia in mice, thereby gaining an edge during its competition with the gut microbiota through an unknown mechanism. Here, we show that by triggering colonie crypt hyperplasia, the C. rodentium T3SS induced an excessive expansion of undifferentiated Ki67-positive epithelial cells, which increased oxygénation of the mucosal surface and drove an aerobic C. rodentium expansion in the colon. Treatment of mice with the -secretase inhibitor dibenzazepine to diminish Notch-driven colonie crypt hyperplasia curtailed the fitness advantage conferred by aerobic respiration during C. rodentium infection. We conclude that C. rodentium uses its T3SS to induce histopathological lesions that generate an intestinal microenvironment in which growth of the pathogen is fueled by aerobic respiration.