Department of Nephrology, The First Hospital of Jilin University, Changchun 130021, China.
Department of Urology, Boston Children's Hospital, Boston, MA 02115, USA.
Toxins (Basel). 2021 Mar 18;13(3):222. doi: 10.3390/toxins13030222.
Shiga toxins (Stxs) are classic bacterial toxins and major virulence factors of toxigenic and enterohemorrhagic (EHEC). These toxins recognize a glycosphingolipid globotriaosylceramide (Gb3/CD77) as their receptor and inhibit protein synthesis in cells by cleaving 28S ribosomal RNA. They are the major cause of life-threatening complications such as hemolytic uremic syndrome (HUS), associated with severe cases of EHEC infection, which is the leading cause of acute kidney injury in children. The threat of Stxs is exacerbated by the lack of toxin inhibitors and effective treatment for HUS. Here, we briefly summarize the Stx structure, subtypes, in vitro and in vivo models, Gb3 expression and HUS, and then introduce recent studies using CRISPR-Cas9-mediated genome-wide screens to identify the host cell factors required for Stx action. We also summarize the latest progress in utilizing and engineering Stx components for biomedical applications.
志贺毒素（Stxs）是经典的细菌毒素，也是产毒性和肠出血性大肠杆菌（EHEC）的主要毒力因子。这些毒素识别糖鞘脂神经节苷脂Gb3/CD77 作为其受体，并通过切割 28S 核糖体 RNA 抑制细胞中的蛋白质合成。它们是危及生命的并发症的主要原因，如溶血性尿毒症综合征（HUS），与 EHEC 感染的严重病例有关，这是儿童急性肾损伤的主要原因。缺乏毒素抑制剂和有效的 HUS 治疗加剧了 Stxs 的威胁。在这里，我们简要总结了 Stx 的结构、亚型、体外和体内模型、Gb3 表达和 HUS，然后介绍了最近利用 CRISPR-Cas9 介导的全基因组筛选来识别 Stx 作用所需的宿主细胞因子的研究。我们还总结了利用和工程 Stx 成分进行生物医学应用的最新进展。
