Institute for Hygiene, University of Münster, D-48149 Münster, Germany.
Glycobiology. 2012 Jun;22(6):849-62. doi: 10.1093/glycob/cws009. Epub 2012 Jan 25.
Shiga toxin (Stx) 2e of Stx-producing Escherichia coli (STEC) represents the major virulence factor responsible for the pig edema disease which is characterized by hemorrhagic lesions, neurological disorders and often fatal outcomes. Stx2e-producing strains from the intestine of slaughtered pigs (n = 3), feces of piglets with postweaning diarrhea or edema disease (n = 12) and feces of humans with asymptomatic infections or mild diarrhea (n = 13) were comparatively analyzed for the binding specificities of Stx2e to glycosphingolipids (GSLs) of the globo-series. Besides equivalent binding towards globotriaosylceramide (Gb3Cer) and globotetraosylceramide (Gb4Cer), we could demonstrate specific interaction of Stx2e preparations from human and porcine STEC isolates with Forssman GSL. Notably, Forssman GSL was recognized neither by structurally closely related Stx2 nor by Stx1 derived from human STEC isolates conferring Stx2e a unique recognition feature. Noteworthy, 7 (54%) of the 13 human and 8 (53%) of the 15 pig Stx2e samples exhibited cytotoxic action towards human brain microvascular endothelial cells. Our findings provide a basis for further exploring the functional role of the promiscuous receptor repertoire of Stx2e and the exact nature of the mechanisms that underlie different pathological outcomes of Stx2e-producing STEC in humans and pigs.
产志贺毒素 2e（Stx2e）的产志贺毒素大肠杆菌（STEC）代表了主要的毒力因子，其导致猪水肿病，其特征为出血性病变、神经紊乱，且通常导致致命后果。我们对屠宰猪肠道（n=3）、仔猪断奶后腹泻或水肿病粪便（n=12）以及无症状感染或轻度腹泻人类粪便（n=13）中的产 Stx2e 菌株进行了比较分析，以研究 Stx2e 对神经节苷脂（GSL）的结合特异性。除了对神经节三酰基半乳糖苷（Gb3Cer）和神经节四酰基半乳糖苷（Gb4Cer）具有等效的结合作用外，我们还可以证明来自人类和猪源 STEC 分离株的 Stx2e 制剂与 Forssman GSL 的特异性相互作用。值得注意的是，结构上密切相关的 Stx2 以及源自人类 STEC 分离株的 Stx1 均不识别 Forssman GSL，从而赋予 Stx2e 独特的识别特征。值得注意的是，13 份人类和 15 份猪 Stx2e 样本中有 7（54%）份和 8（53%）份对人脑血管内皮细胞具有细胞毒性作用。我们的研究结果为进一步探索 Stx2e 混杂受体谱的功能作用以及 Stx2e 产生的 STEC 在人类和猪中导致不同病理结果的确切机制提供了基础。
