An enteric pathogen subverts colonization resistance by evading competition for amino acids in the gut

The microbiota confers host protection by limiting the colonization of pathogenic bacteria in the gut, but the mechanisms by which pathogens overcome colonization resistance remain poorly understood. Using a high-density transposon screen in the enteric pathogen Citrobacter rodentium, we found that the bacterium requires amino acid biosynthesis pathways to colonize conventionally raised mice, but not germ-free or antibiotic-treated animals. These metabolic pathways were induced during infection by the presence of the gut microbiota. Reduced amounts of amino acids were found in the gut of conventionally raised mice compared with germ-free animals. Administration of a high protein diet increased pathogen colonization. Thus, depletion of amino acids by the microbiota limits pathogen colonization, and in turn the pathogen activates amino acid biosynthesis to expand in the presence of the microbiota.