Michael G. DeGroote Institute for Infectious Disease Research, Hamilton, ON, Canada.
Michael G. DeGroote Institute for Infectious Disease Research, Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Hamilton, ON, Canada.
Cell Host Microbe. 2019 Feb 13;25(2):301-312.e5. doi: 10.1016/j.chom.2018.12.010. Epub 2019 Jan 22.
Crohn's disease (CD) is an inflammatory bowel disease influenced by bacteria. Adherent-invasive E. coli (AIEC) is associated with CD, yet the adaptations facilitating AIEC gut colonization are unknown. AIEC isolates exhibit high genetic diversity, suggesting strains evolve independently across different gut environments. We tracked the adaptive evolution of AIEC in a murine model of chronic colonization across multiple hosts and transmission events. We detected evolved lineages that outcompeted the ancestral strain in the host through independent mechanisms. One lineage was hypermotile because of a mobile insertion sequence upstream of the master flagellar regulator, flhDC, which enhanced AIEC invasion and establishment of a mucosal niche. Another lineage outcompeted the ancestral strain through improved use of acetate, a short-chain fatty acid in the gut. The presence of hypermotile and acetate-consuming lineages discriminated E. coli isolated from CD patients from healthy controls, suggesting an evolutionary trajectory that distinguishes AIEC from commensal E. coli.
克罗恩病（CD）是一种受细菌影响的炎症性肠病。黏附侵袭性大肠杆菌（AIEC）与 CD 有关，但促进 AIEC 肠道定植的适应机制尚不清楚。AIEC 分离株表现出高度的遗传多样性，这表明菌株在不同的肠道环境中独立进化。我们在慢性定植的小鼠模型中跟踪 AIEC 的适应性进化，跨越多个宿主和传播事件。我们检测到了通过独立机制在宿主中竞争过祖先菌株的进化谱系。一个谱系由于位于主要鞭毛调控因子 flhDC 上游的移动插入序列而变得超运动，这增强了 AIEC 的侵袭和粘膜生态位的建立。另一个谱系通过更好地利用肠道中的短链脂肪酸乙酸盐来竞争过祖先菌株。具有超运动和消耗乙酸盐能力的谱系的存在可以将从 CD 患者中分离出的大肠杆菌与健康对照区分开来，这表明了一种可以将 AIEC 与共生大肠杆菌区分开来的进化轨迹。
