Elucidation of Shiga-toxigenic Escherichia coli produced Subtilase cytotoxin-induced cell damage mechanism.

枯草杆菌酶细胞毒素（Subtilase cytotoxin，SubAB）是由部分志贺菌大肠杆菌产生的一种AB 5型细胞毒素。A亚基是一种枯草杆菌酶样丝氨酸蛋白酶，切割内质网（ER）伴侣BiP，导致ER应激，其诱导蛋白质合成的短暂抑制和细胞周期停滞在G1期，以及PERK介导的Bax/巴克构象变化，线粒体释放细胞色素c，随后是哺乳动物细胞中的半胱天冬酶依赖性凋亡。此外，我们在小鼠中发现，SubAB诱导小肠出血和凝血功能障碍，其特征是血小板减少，凝血酶原时间延长和活化部分凝血活酶时间。

Subtilase cytotoxin (SubAB) is an AB5 cytotoxin produced by some strains of Shiga-toxigenic Escherichia coli. The A subunit is a subtilase-like serine protease and cleaves an endoplasmic reticulum (ER) chaperone, BiP, leading to ER stress, which induces transient inhibition of protein synthesis and cell cycle arrest at G1 phase, and PERK-mediated Bax/Bak conformational change, cytochrome c release from mitochondria, followed by caspase-dependent apoptosis in mammalian cells. In addition, we showed in mice that SubAB induced small bowel hemorrhage and a coagulopathy characterized by thrombocytopenia, prolonged prothrombin time and activated partial thromboplastin time.