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Host response to the Subtilase cytotoxin produced by locus of enterocyte effacement (LEE)-negative Shiga-toxigenic Escherichia coli (STEC).
Microbiology and Immunology ( IF 1.9 ) Pub Date : 2020-09-09 , DOI: 10.1111/1348-0421.12841
Hiroyasu Tsutsuki 1 , Kohei Ogura 2 , Joel Moss 3 , Kinnosuke Yahiro 4
Affiliation  

Shiga‐toxigenic Escherichia coli (STEC) is a major bacterium responsible for disease resulting from foodborne infection, including bloody diarrhea and hemolytic uremic syndrome. STEC produces important virulence factors such as Shiga toxin (Stx) 1 and/or 2. In the STEC family, some locus of enterocyte effacement‐negative STEC produce two different types of cytotoxins, namely, Stx2 and subtilase cytotoxin (SubAB). The Stx2 and SubAB cytotoxins are structurally similar and composed of one A subunit and pentamer of B subunits. The catalytically active A subunit of SubAB is a subtilase‐like serine protease and specifically cleaves an endoplasmic reticulum (ER) chaperone 78‐kDa glucose‐regulated protein (GRP78/BiP), a monomeric ATPase that is crucial in protein folding and quality control. The B subunit binds to cell surface receptors. SubAB recognizes sialic carbohydrate‐modified cell surface proteins as a receptor. After translocation into cells, SubAB is delivered to the ER, where it cleaves GRP78/BiP. SubAB‐catalyzed BiP cleavage induces ER stress, which causes various cell events including inhibition of protein synthesis, suppression of nuclear factor‐kappa B activation, apoptotic cell death, and stress granules formation. In this review, we describe SubAB, the SubAB receptor, and the mechanism of cell response to the toxin.

中文翻译:

宿主对由肠上皮细胞侵染(LEE)阴性志贺毒素大肠杆菌(STEC)产生的枯草杆菌蛋白酶细胞毒素的反应。

志贺毒素大肠杆菌(STEC)是导致食源性感染(包括血性腹泻和溶血性尿毒症综合征)引起疾病的主要细菌。STEC产生重要的毒力因子,例如志贺毒素(Stx)1和/或2。在STEC家族中,肠上皮细胞阴性的STEC的某些基因座产生两种不同类型的细胞毒素,即Stx2和枯草杆菌蛋白酶细胞毒素(SubAB)。Stx2和SubAB细胞毒素的结构相似,由一个A亚基和一个B亚基的五聚体组成。SubAB的催化活性A亚基是一种类似枯草杆菌蛋白酶的丝氨酸蛋白酶,可特异性裂解内质网伴侣蛋白78-kDa葡萄糖调节蛋白(GRP78 / BiP),这是一种在蛋白质折叠和质量控制中至关重要的单体ATPase。B亚基与细胞表面受体结合。SubAB将唾液糖修饰的细胞表面蛋白识别为受体。易位进入细胞后,SubAB被递送至ER,在此处切割GRP78 / BiP。SubAB催化的BiP裂解诱导内质网应激,从而导致各种细胞事件,包括抑制蛋白质合成,抑制核因子κB活化,凋亡细胞死亡和应激颗粒形成。在这篇综述中,我们描述了SubAB,SubAB受体以及细胞对毒素的反应机制。
更新日期:2020-10-30
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