The StcE metalloprotease of enterohaemorrhagic Escherichia coli reduces the inner mucus layer and promotes adherence to human colonic epithelium ex vivo.
The StcE metalloprotease of enterohaemorrhagic Escherichia coli reduces the inner mucus layer and promotes adherence to human colonic epithelium ex vivo.
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DOI：
10.1111/cmi.12717
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发表时间：
2017-06
影响因子：
3.4
通讯作者：
Schüller S
中科院分区：
文献类型：
--
作者：
Hews CL;Tran SL;Wegmann U;Brett B;Walsham ADS;Kavanaugh D;Ward NJ;Juge N;Schüller S
肠出血性大肠杆菌（EHEC）是一种主要的食源性致病菌，通过形成附着/消退病变而与人体结肠上皮紧密粘附。为了到达上皮表面，EHEC必须穿透保护结肠上皮的厚粘液层。在这项研究中，我们使用产生粘蛋白的LS 174 T结肠癌细胞和人类结肠粘膜活检来研究EHEC如何与肠粘液层相互作用。与粘蛋白缺陷型结肠癌细胞系相比，LS 174 T细胞中EHEC结合和附着/消失病变形成的水平更高，并且初始粘附与鞭毛蛋白、大肠杆菌普通菌毛或长极菌毛的存在无关。虽然肠出血性大肠杆菌感染不影响分泌粘蛋白的基因表达，但它导致MUC 2糖蛋白水平降低。这种作用依赖于分泌的金属蛋白酶StcE的催化活性，其减少了内粘液层，从而促进了EHEC在体外和离体中与上皮的接触和结合。由于缺乏有效的治疗方法来对抗肠出血性大肠杆菌感染，StcE可能是未来治疗和预防策略的合适靶点。
Enterohaemorrhagic Escherichia coli (EHEC) is a major foodborne pathogen and tightly adheres to human colonic epithelium by forming attaching/effacing lesions. To reach the epithelial surface, EHEC must penetrate the thick mucus layer protecting the colonic epithelium. In this study, we investigated how EHEC interacts with the intestinal mucus layer using mucin‐producing LS174T colon carcinoma cells and human colonic mucosal biopsies. The level of EHEC binding and attaching/effacing lesion formation in LS174T cells was higher compared to mucin‐deficient colon carcinoma cell lines, and initial adherence was independent of the presence of flagellin, Escherichia coli common pilus, or long polar fimbriae. Although EHEC infection did not affect gene expression of secreted mucins, it resulted in reduced MUC2 glycoprotein levels. This effect was dependent on the catalytic activity of the secreted metalloprotease StcE, which reduced the inner mucus layer and thereby promoted EHEC access and binding to the epithelium in vitro and ex vivo. Given the lack of efficient therapies against EHEC infection, StcE may represent a suitable target for future treatment and prevention strategies.