Wang Hui, Paton James C, Paton Adrienne W
School of Molecular and Biomedical Science, University of Adelaide, Australia.
J Infect Dis. 2007 Oct 1;196(7):1093-101. doi: 10.1086/521364. Epub 2007 Aug 22.
Subtilase cytotoxin (SubAB) is the prototype of a recently discovered AB(5) cytotoxin family produced by certain strains of Shiga toxigenic Escherichia coli (STEC). The catalytic A subunit is a highly specific subtilase-like serine protease that cleaves the endoplasmic reticulum chaperone BiP. The toxin is lethal for mice, but the pathology it induces is poorly understood. Here, we show that intraperitoneal injection of SubAB causes microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment in mice--characteristics typical of Shiga toxin-induced hemolytic uremic syndrome. SubAB caused extensive microvascular thrombosis and other histologic damage in the brain, kidneys, and liver, as well as dramatic splenic atrophy. Peripheral blood leukocyte levels were increased at 24 h; there was also significant neutrophil infiltration in the liver, kidneys, and spleen and toxin-induced apoptosis at these sites. These findings raise the possibility that SubAB directly contributes to pathology in humans infected with strains of STEC that produce both Shiga toxin and SubAB.
枯草杆菌蛋白酶细胞毒素（SubAB）是由某些产志贺毒素大肠杆菌（STEC）菌株产生的一种最近发现的AB(5)细胞毒素家族的原型。催化性A亚基是一种高度特异性的枯草杆菌蛋白酶样丝氨酸蛋白酶，可切割内质网伴侣蛋白BiP。该毒素对小鼠具有致死性，但其诱导的病理学机制尚不清楚。在此，我们表明腹腔注射SubAB会导致小鼠微血管病性溶血性贫血、血小板减少和肾功能损害——这些是志贺毒素诱导的溶血性尿毒症综合征的典型特征。SubAB在脑、肾和肝脏中引起广泛的微血管血栓形成和其他组织学损伤，以及显著的脾萎缩。外周血白细胞水平在24小时时升高；肝脏、肾脏和脾脏中也有明显的中性粒细胞浸润以及这些部位的毒素诱导的细胞凋亡。这些发现增加了SubAB直接导致感染同时产生志贺毒素和SubAB的STEC菌株的人类发病的可能性。
