Resident and Engrafting E. coli Populations Expand Through Dissimilar Pathways in the Inflamed Gut

Abstract Intestinal inflammation increases the abundance of Enterobacteriaceae in the gastrointestinal tract by several orders of magnitude. These population expansions, or blooms, are associated with disease progression and have been suggested to exacerbate intestinal pathologies in some settings. Murine studies have shown that during the early stages of Escherichia coli colonization, i.e., during engraftment, inflammation enhances fitness through processes that depend on Moco, an enzyme cofactor found in a variety of oxidoreductases that consists of molybdenum coordinated by a pterin molecule. Using a murine commensal E. coli isolate and a DSS-induced colitis model in mice, we investigated whether Moco is also important for blooms of E. coli that are part of the resident microbiota, that is, for E. coli that have engrafted well before the onset of inflammation. We show that resident wild-type and Moco - E. coli exhibit comparable expansions in response to inflammation, indicating that, in this context, Moco-dependent processes such as nitrate respiration or formate oxidation were not important for inflammation-induced blooms. We find that Moco is important, however, for E. coli colonization in the absence of inflammation, suggesting that alternative respiratory pathways or other Moco-dependent processes are necessary for E. coli colonization of a healthy murine gut. Our findings demonstrate that the mechanisms underlying inflammation-induced blooms can depend on the temporal relationship between engraftment and inflammation, and also highlight the importance of considering colonization stage in identifying and interpreting the factors that affect the fitness of microbes colonizing the intestine.