Rivera-Chávez Fabian, Zhang Lillian F, Faber Franziska, Lopez Christopher A, Byndloss Mariana X, Olsan Erin E, Xu Gege, Velazquez Eric M, Lebrilla Carlito B, Winter Sebastian E, Bäumler Andreas J
Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
Department of Chemistry, College of Letters and Sciences, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
Cell Host Microbe. 2016 Apr 13;19(4):443-54. doi: 10.1016/j.chom.2016.03.004.
The mammalian intestine is host to a microbial community that prevents pathogen expansion through unknown mechanisms, while antibiotic treatment can increase susceptibility to enteric pathogens. Here we show that streptomycin treatment depleted commensal, butyrate-producing Clostridia from the mouse intestinal lumen, leading to decreased butyrate levels, increased epithelial oxygenation, and aerobic expansion of Salmonella enterica serovar Typhimurium. Epithelial hypoxia and Salmonella restriction could be restored by tributyrin treatment. Clostridia depletion and aerobic Salmonella expansion were also observed in the absence of streptomycin treatment in genetically resistant mice but proceeded with slower kinetics and required the presence of functional Salmonella type III secretion systems. The Salmonella cytochrome bd-II oxidase synergized with nitrate reductases to drive luminal expansion, and both were required for fecal-oral transmission. We conclude that Salmonella virulence factors and antibiotic treatment promote pathogen expansion through the same mechanism: depletion of butyrate-producing Clostridia to elevate epithelial oxygenation, allowing aerobic Salmonella growth.
哺乳动物的肠道是一个微生物群落的宿主，该群落通过未知机制阻止病原体扩散，而抗生素治疗会增加对肠道病原体的易感性。在这里，我们表明链霉素治疗会使小鼠肠腔中产生丁酸盐的共生梭状芽孢杆菌减少，导致丁酸盐水平降低、上皮细胞氧合增加以及肠炎沙门氏菌血清型鼠伤寒沙门氏菌的需氧性扩张。三丁酸甘油酯治疗可恢复上皮细胞缺氧和沙门氏菌限制。在基因抗性小鼠中，即使没有链霉素治疗也观察到梭状芽孢杆菌减少和需氧性沙门氏菌扩张，但动力学较慢，并且需要功能性沙门氏菌III型分泌系统的存在。沙门氏菌细胞色素bd-II氧化酶与硝酸盐还原酶协同作用以驱动肠腔扩张，两者都是粪-口传播所必需的。我们得出结论，沙门氏菌毒力因子和抗生素治疗通过相同机制促进病原体扩张：减少产生丁酸盐的梭状芽孢杆菌以提高上皮细胞氧合，从而使需氧性沙门氏菌生长。
