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的蛋白质是C. difficile毒素B的结肠上皮受体

Liang Tao^1,2, Jie Zhang^1,2, Paul Meraner³

¹Department of Urology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

|September 30, 2016

概括

困难毒素B (TcdB) 使用Wnt受体,特别是Frizzled蛋白 (FZD),作为其进入细胞的入口. 阻断FZD1,FZD2和FZD7显著降低了TcdB

科学领域:

微生物学
细胞生物学
分子生物学

背景情况:

困难菌毒素B (TcdB) 是困难菌感染的一个关键因素.
识别TcdB受体对于理解它的发病过程至关重要.

研究的目的:

为了确定宿主细胞对Clostridium difficile毒素B (TcdB) 的受体.
阐明TcdB进入宿主细胞并破坏细胞功能的机制.

主要方法:

使用CRISPR-Cas9介导的全基因组选来识别TcdB受体.
进行了结合测定,以确定TcdB与已识别的受体的亲和力.
使用了包括三重敲击细胞和器官模型在内的细胞耐药性测试.
在淘汰小鼠的体内研究评估了对TcdB诱导损伤的敏感性.

主要成果:

确定了Wnt受体Frizzled家族 (FZDs) 的成员为TcdB的关键受体.
TcdB与FZDs的氨酸丰富域 (CRD) 结合,对FZD1,FZD2和FZD7的亲和力最高.
TcdB与FZD的结合与Wnt信号竞争,抑制Wnt通路.
在FZD1/ 2/ 7三重淘汰细胞和FZD7淘汰小鼠模型中显示出对TcdB的显著耐药性.
重组FZD2-CRD抑制了TcdB与结肠表皮的结合.

结论:

状蛋白 (FZDs) 是结肠表皮中Clostridium difficile毒素B (TcdB) 的生理相关受体.
它使用FZD来启动细胞损伤, 使它们成为潜在的治疗点.

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