Translocated EspF protein from enteropathogenic Escherichia coli disrupts host intestinal barrier function
Translocated EspF protein from enteropathogenic Escherichia coli disrupts host intestinal barrier function
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DOI：
10.1172/jci11138
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发表时间：
2001-03-01
影响因子：
15.9
通讯作者：
Hecht, G
中科院分区：
文献类型：
--
作者：
McNamara, BP;Koutsouris, A;Hecht, G
肠致病性大肠杆菌（EPEC）是发展中国家婴儿腹泻的重要原因，其诱导症状的机制尚未确定。EPEC具有III型分泌系统，其特征性的附着和消失变化所需，这些变化改变宿主细胞的细胞骨架和顶端表面。极化的肠上皮细胞单层被EPEC感染导致跨上皮电阻的损失，这也需要III型分泌系统。我们在这里证明，EspF，蛋白质聊天EPEC通过III型分泌系统分泌，是不需要定量和定性典型的附着和消退病变形成肠上皮细胞。然而，对于跨上皮电阻的损失、单层渗透性的增加和紧密连接相关蛋白闭合蛋白的重新分布，EspF是以剂量依赖性方式所需要的。此外，对表达EspF-腺苷酸环化酶融合蛋白的EPEC菌株的分析表明，EspF通过III型分泌系统易位到宿主细胞的细胞质中，结果：通过免疫荧光显微镜证实。这些研究表明，EspF作为一种效应蛋白原，在不参与附着和消除病变形成的情况下破坏肠屏障功能，具有新的作用。
The mechanisms by which enteropathogenic Escherichia coli (EPEC), an important cause of diarrhea among infants in developing countries, induce symptoms are not defined. EPEC have a type III secretion system required for characteristic attaching and effacing changes that modify the cytoskeleton and apical surface of host cells. Infection of polarized intestinal epithelial cell monolayers by EPEC leads to a loss of transepithelial electrical resistance, which also requires the type III secretion system. We demonstrate here that EspF, a protein chat is secreted by EPEC via the type III secretion system, is not required for quantitatively and qualitatively typical attaching and effacing lesion formation in intestinal epithelial cells. However, EspF is required in a dose-dependent fashion for the loss of transepithelial electrical resistance, for increased monolayer permeability, and for redistribution of the tight junction-associated protein occludin, Furthermore, the analysis of EPEC strains expressing EspF-adenylate cyclase fusion proteins indicates that EspF is translocated via the type III secretion system to the cytoplasm of host cells, a result: confirmed by immunofluorescence microscopy. These studies suggest a novel role for EspF as an effector pro rein that disrupts intestinal barrier function without involvement in attaching and effacing lesion formation.