Citrobacter rodentium–host–microbiota interactions: immunity, bioenergetics and metabolism

Citrobacter rodentium is an extracellular enteric mouse-specific pathogen used to model infections with human pathogenic Escherichia coli and inflammatory bowel disease. C. rodentium injects type III secretion system effectors into intestinal epithelial cells (IECs) to target inflammatory, metabolic and cell survival pathways and establish infection. While the host responds to infection by activating innate and adaptive immune signalling, required for clearance, the IECs respond by rapidly shifting bioenergetics to aerobic glycolysis, which leads to oxygenation of the epithelium, an instant expansion of mucosal-associated commensal Enterobacteriaceae and a decline of obligate anaerobes. Moreover, infected IECs reprogramme intracellular metabolic pathways, characterized by simultaneous activation of cholesterol biogenesis, import and efflux, leading to increased serum and faecal cholesterol levels. In this Review we summarize recent advances highlighting the intimate relationship between C. rodentium pathogenesis, metabolism and the gut microbiota. Citrobacter rodentium, an extracellular mouse-specific enteric pathogen, provides a robust model for the study of physiological host–pathogen–microbiota interactions. In this Review, Frankel and colleagues highlight how the C. rodentium model has advanced our understanding of enteric infections and inflammatory bowel disease, in particular changes to host metabolism and inflammation.