Department of Molecular Infectiology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Microb Pathog. 2011 Mar-Apr;50(3-4):159-67. doi: 10.1016/j.micpath.2011.01.002. Epub 2011 Jan 11.
Subtilase cytotoxin (SubAB) is an AB(5) type toxin produced by a subset of Shiga-toxigenic Escherichia coli. The A subunit is a subtilase-like serine protease and cleaves an endoplasmic reticulum chaperone BiP. The B subunit binds to a receptor on the cell surface. Although SubAB is lethal for mice, the cause of death is not clear. In this study, we demonstrate in mice that SubAB induced small bowel hemorrhage and a coagulopathy characterized by thrombocytopenia, prolonged prothrombin time and activated partial thromboplastin time. SubAB also induced inflammatory changes in the small intestine as detected by ¹⁸F-fluoro-2-deoxy-d-glucose positron emission tomography imaging and histochemical analysis. Using RT-PCR and ELISA, SubAB was shown to increase interleukin-6 in a time-dependent manner. Thus, our results indicate that death in SubAB-treated mice may be associated with severe inflammatory response and hemorrhage of the small intestine, accompanied by coagulopathy and IL6 production.
类枯草溶菌素细胞毒素（SubAB）是由一组产志贺毒素大肠杆菌产生的 AB(5)型毒素。A 亚基是一种类枯草溶菌素丝氨酸蛋白酶，可切割内质网伴侣蛋白 BiP。B 亚基结合在细胞表面的受体上。尽管 SubAB 对小鼠是致命的，但死亡原因尚不清楚。在这项研究中，我们在小鼠中证明，SubAB 诱导小肠出血和以血小板减少症、凝血酶原时间延长和活化部分凝血活酶时间延长为特征的凝血功能障碍。SubAB 还通过¹⁸F-氟-2-脱氧-d-葡萄糖正电子发射断层扫描成像和组织化学分析检测到在小肠中诱导炎症变化。通过 RT-PCR 和 ELISA，SubAB 被证明以时间依赖性方式增加白细胞介素-6。因此，我们的结果表明，SubAB 处理的小鼠死亡可能与小肠严重炎症反应和出血、凝血功能障碍和 IL6 产生有关。
