Commensal Enterobacteriaceae Protect against Salmonella Colonization through Oxygen Competition

Abstract

Neonates are highly susceptible to infection with enteric pathogens, but the underlying mechanisms are not resolved. We show that neonatal chick colonization with Salmonella enterica serovar Enteritidisrequires a virulence-factor-dependent increase inepithelial oxygenation, which drives pathogen expansion by aerobic respiration. Co-infection experiments with an Escherichia coli strain carrying an oxygen-sensitive reporter suggest that S. Enteritidis competes with commensal Enterobacteriaceae for oxygen. A combination of Enterobacteriaceae and spore-forming bacteria, but not colonization with either community alone, confers colonization resistance against S.Enteritidis in neonatal chicks, phenocopying germ-free mice associated with adultchicken microbiota. Combining spore-forming bacteria with a probiotic E.coli isolate protects germ-free mice from pathogen colonization, but theprotection is lost when the ability to respire oxygen under micro-aerophilic conditions is genetically ablated in E.coli. These results suggest that commensal Enterobacteriaceae contribute to colonization resistance by competing with S. Enteritidis for oxygen, a resource critical for pathogen expansion.