Institute for Hygiene, University of Münster, D-48149 Münster, Germany.
Institute for Hygiene, University of Münster, D-48149 Münster, Germany; Interdisciplinary Center for Clinical Research (IZKF), University of Münster, D-48149 Münster, Germany.
Int J Med Microbiol. 2018 Dec;308(8):1073-1084. doi: 10.1016/j.ijmm.2018.09.003. Epub 2018 Sep 8.
Shiga toxin (Stx)-mediated injury of the kidneys and the brain represent the major extraintestinal complications in humans upon infection by enterohemorrhagic Escherichia coli (EHEC). Damage of renal and cerebral endothelial cells is the key event in the pathogenesis of the life-threatening hemolytic uremic syndrome (HUS). Stxs are AB toxins and the B-pentamers of the two clinically important Stx subtypes Stx1a and Stx2a preferentially bind to the glycosphingolipid globotriaosylceramide (Gb3Cer, Galα4Galβ4Glcβ1Cer) and to less extent to globotetraosylceramide (Gb4Cer, GalNAcβ3Galα4Galβ4Glcβ1), which are expected to reside in lipid rafts in the plasma membrane of the human endothelium. This review summarizes the current knowledge on the Stx glycosphingolipid receptors and their lipid membrane ensemble in primary human brain microvascular endothelial cells (pHBMECs) and primary human renal glomerular endothelial cells (pHRGECs). Increasing knowledge on the precise initial molecular mechanisms by which Stxs interact with cellular targets will help to develop specific therapeutics and/or preventive measures to combat EHEC-caused diseases.
志贺毒素（Stx）介导的肾和脑损伤是人类感染肠出血性大肠杆菌（EHEC）后主要的肠道外并发症。肾脏和脑内皮细胞的损伤是溶血性尿毒症综合征（HUS）这一致命疾病发病机制中的关键事件。Stx 是 AB 毒素，两种临床上重要的 Stx 亚型 Stx1a 和 Stx2a 的 B-五聚体优先结合糖鞘脂神经节苷脂 GM1（Gb3Cer，Galα4Galβ4Glcβ1Cer），并在较小程度上结合神经节苷脂 GM2（Gb4Cer，GalNAcβ3Galα4Galβ4Glcβ1），预计它们存在于人内皮细胞膜的脂筏中。本文综述了 Stx 糖鞘脂受体及其在原代人脑微血管内皮细胞（pHBMECs）和原代人肾小球内皮细胞（pHRGECs）中的脂质膜整体的最新知识。对 Stx 与细胞靶标相互作用的确切初始分子机制的深入了解将有助于开发针对 EHEC 引起的疾病的特异性治疗方法和/或预防措施。
