两成分系统调节脆弱拟杆菌毒素以维持肠道内稳态并预防致命疾病。
A Two-Component System Regulates Bacteroides fragilis Toxin to Maintain Intestinal Homeostasis and Prevent Lethal Disease.
机构信息
University of Chicago, Department of Microbiology, Chicago, IL 60637, USA; University of Chicago, Interdisciplinary Scientist Training Program, Chicago, IL 60637, USA.
University of Chicago, Department of Microbiology, Chicago, IL 60637, USA; University of Chicago, Departments of Pediatrics and Microbiology, Chicago, IL 60637, USA.
出版信息
Cell Host Microbe. 2017 Oct 11;22(4):443-448.e5. doi: 10.1016/j.chom.2017.08.007. Epub 2017 Sep 21.
Intestinal microbes are recognized for their role in human disease. Enterotoxigenic Bacteroides fragilis (ETBF) has been implicated in inflammatory bowel disease and colorectal cancer; however, colonization alone is insufficient to cause these illnesses. We hypothesized that homeostasis in healthy carriers is maintained by colonic mucus, the major constituent of which is the glycoprotein Muc2. We found that Muc2-deficient mice succumb to lethal disease from ETBF colonization in a B. fragilis toxin (BFT)-dependent manner. We identify a toxin regulator, the two-component system RprXY, which suppresses BFT expression in vitro and in vivo. Overexpression of either component was sufficient to prevent lethal disease in Muc2-deficient mice. Our studies demonstrate that homeostasis in the context of ETBF colonization is dependent on a dynamic interaction between intestinal mucus, a bacterial toxin, and a toxin regulatory system. Regulation of virulence may offer a therapeutic target to maintain intestinal homeostasis in susceptible patients.
肠道微生物因其在人类疾病中的作用而被人们所认识。产肠毒素脆弱拟杆菌（ETBF）已被牵连到炎症性肠病和结直肠癌中；然而，单独定植不足以导致这些疾病。我们假设健康携带者的体内平衡是由结肠黏液维持的，而结肠黏液的主要成分是糖蛋白 Muc2。我们发现，Muc2 缺陷型小鼠在 B. fragilis 毒素（BFT）依赖性方式下，由于 ETBF 定植而死于致命疾病。我们鉴定出一种毒素调节剂，即双组分系统 RprXY，它在体外和体内抑制 BFT 的表达。两种成分中的任何一种的过度表达都足以防止 Muc2 缺陷型小鼠发生致命疾病。我们的研究表明，在 ETBF 定植的情况下，体内平衡依赖于肠道黏液、细菌毒素和毒素调节系统之间的动态相互作用。对毒力的调节可能为维持易感患者的肠道内平衡提供一个治疗靶点。
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