Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, CA 95616, USA.
Department of Animal Science, University of California, Davis, Davis, CA 95616, USA.
Cell Host Microbe. 2019 Jan 9;25(1):128-139.e5. doi: 10.1016/j.chom.2018.12.003.
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 Enteritidis requires a virulence-factor-dependent increase in epithelial 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 adult chicken microbiota. Combining spore-forming bacteria with a probiotic E. coli isolate protects germ-free mice from pathogen colonization, but the protection 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.
新生儿极易受到肠道病原体的感染，但其中的潜在机制尚未得到解决。我们发现，鸡仔的沙门氏菌肠炎血清型定植需要依赖于毒力因子的增加来促进上皮组织的氧合作用，进而通过需氧呼吸促进病原体的扩张。与携带氧敏感报告基因的大肠杆菌共感染实验表明，肠炎沙门氏菌与共生的肠杆菌科细菌竞争氧气。肠杆菌科和产孢子细菌的组合，而不是单独定植这两种菌群，赋予了新生鸡仔抵抗肠炎沙门氏菌定植的能力，这与与成年鸡的微生物群相关的无菌小鼠类似。将产孢子细菌与益生菌大肠杆菌分离株结合使用可保护无菌小鼠免受病原体定植，但当大肠杆菌中遗传消除了在微需氧条件下呼吸氧气的能力时，这种保护作用就会丧失。这些结果表明，共生的肠杆菌科通过与肠炎沙门氏菌竞争氧气来促进定植抵抗，而氧气是病原体扩张的关键资源。
