StcE, a metalloprotease secreted by Escherichia coli O157:H7, specifically cleaves C1 esterase inhibitor
StcE, a metalloprotease secreted by Escherichia coli O157:H7, specifically cleaves C1 esterase inhibitor
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DOI：
10.1046/j.1365-2958.2002.02997.x
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发表时间：
2002-07-01
影响因子：
3.6
通讯作者：
Welch, RA
中科院分区：
文献类型：
--
作者：
Lathem, WW;Grys, TE;Welch, RA
大肠杆菌O 157：H7引起腹泻、出血性结肠炎和溶血性尿毒综合征。我们鉴定了大肠杆菌pO 157毒力质粒上编码的一种以前未知功能的蛋白。coli O 157：H7，其是第一个被描述的特异性切割丝氨酸蛋白酶抑制剂家族成员C1酯酶抑制剂（C1-INH）的蛋白酶。该蛋白质，命名为StcE，用于来自E HEC的C1酯酶抑制剂的分泌蛋白酶（以前称为Tagn），切割C1-INH以产生（独特的）约60-65 kDa的片段。StcE不消化其他丝氨酸蛋白酶抑制剂、细胞外基质蛋白或通用蛋白酶靶标。我们还观察到StcE引起培养的人T细胞的聚集，但不引起巨噬细胞样细胞或B细胞的聚集。在共有金属蛋白酶活性位点内的StcE位置435处用天冬氨酸取代谷氨酸消除了其消化C1-INH和聚集T细胞的能力。StcE由pO 157编码的etp II型分泌途径分泌，细胞外StcE水平由LEE编码的调节因子Ler正向调节。在一例大肠杆菌患儿粪便中检测到StcE抗原和活性。coliO 157：H7感染，证实StcE在人类疾病过程中表达。StcE裂解C1-INH可能会引起局部促炎和凝血反应，导致组织损伤、肠水肿和血栓形成异常。
Escherichia coli O157:H7 causes diarrhoea, haemorrhagic colitis, and the haemolytic uraemic syndrome. We have identified a protein of previously unknown function encoded on the pO157 virulence plasmid of E. coli O157:H7, which is the first described protease that specifically cleaves C1 esterase inhibitor (C1-INH), a member of the serine protease inhibitor family. The protein, named StcE for secreted protease of C1 esterase inhibitor from E HEC (formerly Tagn), cleaves C1-INH to produce (unique) approximate to 60-65 kDa fragments. StcE does not digest other serine protease inhibitors, extracellular matrix proteins or universal protease targets. We also observed that StcE causes the aggregation of cultured human T cells but not macrophage-like cells or B cells. Substitution of aspartic acid for glutamic acid at StcE position 435 within the consensus metalloprotease active site ablates its abilities to digest C1-INH and to aggregate T cells. StcE is secreted by the etp type II secretion pathway encoded on pO157, and extracellular StcE levels are positively regulated by the LEE-encoded regulator, Ler. StcE antigen and activity were detected in the faeces of a child with an E. coli O157:H7 infection, demonstrating the expression of StcE during human disease. Cleavage of C1-INH by StcE could plausibly cause localized pro-inflammatory and coagulation responses resulting in tissue damage, intestinal oedema and thrombotic abnormalities.