Epithelial-Derived Reactive Oxygen Species Enable AppBCX-Mediated Aerobic Respiration of Escherichia coli during Intestinal Inflammation

The intestinal epithelium separates host tissue and gut-associated microbial communities. During inflammation, the host releases reactive oxygen and nitrogen species as an antimicrobial response. The impact of these radicals on gut microbes is incompletely understood. We discovered that the cryptic appBCX genes, predicted to encode a cytochrome bd-II oxidase, conferred a fitness advantage for E. coli in chemical and genetic models of non-infectious colitis. This fitness advantage was absent in mice that lacked epithelial NADPH oxidase 1 (NOX1) activity. In laboratory growth experiments, supplementation with exogenous hydrogen peroxide enhanced E. coli growth through AppBCX-mediated respiration in a catalase-dependent manner. We conclude that epithelial-derived reactive oxygen species are degraded in the gut lumen, which gives rise to molecular oxygen that supports the aerobic respiration of E. coli. This work illustrates how epithelial host responses intersect with gut microbial metabolism in the context of gut inflammation. [Display omitted] •AppBCX promotes the outgrowth of E. coli in murine models of gut inflammation•AppBCX respiration requires reactive oxygen species produced by epithelial NOX1•Hydrogen peroxide, detoxified to oxygen, supports AppBCX respiration in vitro During inflammation, the intestinal epithelium produces antimicrobial products to impede bacterial growth. Chanin et al., report that one of these antimicrobial products, reactive oxygen species, also promotes the outgrowth of E. coli. Detoxification of inflammatory reactive oxygen species through AppBCX allows E. coli to respire in an otherwise anaerobic environment.