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 find that the bacterium requires amino acid biosynthesis pathways to colonize conventionally raised mice, but not germ-free or antibiotic-treated animals. These metabolic pathways are induced during infection by the presence of the gut microbiota. Reduced amounts of amino acids are found in the guts of conventionally raised mice compared with germ-free animals. Dietary administration of high protein increases amino acid levels in the gut and promotes pathogen colonization. Thus, the 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.

微生物群通过限制肠道中病原菌的定植来提供宿主保护，但病原体克服定植抗性的机制仍然知之甚少。在肠道病原体柠檬酸杆菌中使用高密度转座子筛选，我们发现这种细菌需要氨基酸生物合成途径来定殖常规饲养的小鼠，而不是无菌或抗生素处理的动物。这些代谢途径是在感染期间由肠道微生物群的存在诱导的。与无菌动物相比，常规饲养的小鼠肠道中发现的氨基酸含量减少。高蛋白的膳食管理会增加肠道中的氨基酸水平并促进病原体定植。因此，微生物群对氨基酸的消耗限制了病原体的定殖，反过来，病原体在微生物群存在的情况下激活氨基酸生物合成以扩大。