Virulence factors enhance Citrobacter rodentium expansion through aerobic respiration

Abstract

Citrobacter rodentium uses a type III secretion system (T3SS) to induce colonic 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 colonic crypt hyperplasia, the C. rodentium T3SS induced an excessive expansion of undifferentiated Ki67-positive epithelial cells, which increased oxygenation of the mucosal surface and drove an aerobic C. rodentium expansion in the colon. Treatment of mice with the γ-secretase inhibitor dibenzazepine to diminish Notch-driven colonic 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.

A Two-Component System Regulates Bacteroides Fragilis Toxin to Maintain Intestinal Homeostasis and Prevent Lethal Disease

“…Genetic recalibration of a toxin-regulatory sense/response system thus restores balance to a hostmicrobe interaction that may favor development of an injurious state. These findings lend experimental support to the "damage-response framework of microbial pathogenesis," in which the state of either health or disease is a product of the exquisite interaction between a microorganism and its host (Casadevall and Pirofski, 2003).Host injury has been described as a competitive strategy for several pathogens including Salmonella enterica serovar Typhimurium and Citrobacter rodentium (Faber et al, 2016;Lopez et al, 2016). B. fragilis differs from these organisms in several important respects, including its ubiquitous presence and stability within healthy human microbiota (Newton et al, 2015).…”

“…Host injury has been described as a competitive strategy for several pathogens including Salmonella enterica serovar Typhimurium and Citrobacter rodentium (Faber et al, 2016;Lopez et al, 2016). B. fragilis differs from these organisms in several important respects, including its ubiquitous presence and stability within healthy human microbiota (Newton et al, 2015).…”

TheBacteroides fragilispathogenicity island links virulence and strain competition

“…Enteric microbes have been described to modify this variable with virulence factors for the selective benefit of their growth. 26 Together with a bfpai-dependent advantage during competitive colonization, these data revealing environmental regulation of BFT indicate B. fragilis may fit within such a paradigm.…”

Community metabolic modeling approaches to understanding the gut microbiome: Bridging biochemistry and ecology

“…However, not all data support this model. In mice the enteric pathogen Citrobacter rodentium increases oxygenation of the mucosal surface of the intestine, allowing the aerobic C. rodentium to proliferate in the colon, as we might predict—but despite higher levels of oxygen, Clostridia species increase in abundance[85]. Community metabolic models that incorporate the oxygen gradient are needed to help us better understand these perplexing findings.…”