Citrobacter amalonaticus Inhibits the Growth of Citrobacter rodentium in the Gut Lumen.
Citrobacter amalonaticus Inhibits the Growth of Citrobacter rodentium in the Gut Lumen.
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DOI：
10.1128/mbio.02410-21
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发表时间：
2021-10-26
期刊：
影响因子：
6.4
通讯作者：
Frankel G
中科院分区：
文献类型：
--
作者：
Mullineaux-Sanders C;Carson D;Hopkins EGD;Glegola-Madejska I;Escobar-Zepeda A;Browne HP;Lawley TD;Frankel G
肠道微生物区系在肠道病原体的易感性中起着至关重要的作用，其中包括轮状柠檬酸杆菌，一种定植于结肠粘膜的模型小鼠细胞外病原体。不同品系的小鼠轮状芽胞杆菌感染结果不同，C57BL/6和C3H/HEN小鼠分别清除和屈服于感染。卡那霉素(Kan)在C57BL/6小鼠感染耐Kan罗氏杆菌的高峰期治疗可使病原体从结肠粘膜和盲肠重新定位到盲肠腔内容物；停止Kan治疗可使病原体迅速清除。我们现在发现，在C3H/HEN小鼠中，在Kan诱导的轮状念珠菌移位到盲肠后，病原体在没有持续抗生素治疗的情况下稳定地在65%的小鼠的盲肠腔内定居，这种现象我们称之为抗生素诱导的细菌共生(AIBC)。AIBC齿状念珠菌对宿主的耐受性良好，几乎没有炎症的迹象；传代后的AIBC齿状念珠菌强势感染幼龄C3H/HEN小鼠，表明AIBC状态是短暂的，不选择遗传上无毒的齿状念珠菌突变体。停用抗生素后，35%的C3H/HEN小鼠能够阻止轮状芽胞杆菌在肠腔内的共生。这些小鼠表现出一种共生物种--柠檬柠檬酸杆菌的繁殖，它在体外以接触依赖的方式抑制轮状芽胞杆菌的生长，在体内抑制轮状芽胞杆菌的管腔生长。总体而言，我们的数据表明，共生物种可以对密切相关的致病物种产生定植抗性。
The gut microbiota plays a crucial role in susceptibility to enteric pathogens, including Citrobacter rodentium, a model extracellular mouse pathogen that colonizes the colonic mucosa. C. rodentium infection outcomes vary between mouse strains, with C57BL/6 and C3H/HeN mice clearing and succumbing to the infection, respectively. Kanamycin (Kan) treatment at the peak of C57BL/6 mouse infection with Kan-resistant C. rodentium resulted in relocalization of the pathogen from the colonic mucosa and cecum to solely the cecal luminal contents; cessation of the Kan treatment resulted in rapid clearance of the pathogen. We now show that in C3H/HeN mice, following Kan-induced displacement of C. rodentium to the cecum, the pathogen stably colonizes the cecal lumens of 65% of the mice in the absence of continued antibiotic treatment, a phenomenon that we term antibiotic-induced bacterial commensalization (AIBC). AIBC C. rodentium was well tolerated by the host, which showed few signs of inflammation; passaged AIBC C. rodentium robustly infected naive C3H/HeN mice, suggesting that the AIBC state is transient and did not select for genetically avirulent C. rodentium mutants. Following withdrawal of antibiotic treatment, 35% of C3H/HeN mice were able to prevent C. rodentium commensalization in the gut lumen. These mice presented a bloom of a commensal species, Citrobacter amalonaticus, which inhibited the growth of C. rodentium in vitro in a contact-dependent manner and the luminal growth of AIBC C. rodentium in vivo. Overall, our data suggest that commensal species can confer colonization resistance to closely related pathogenic species.