Cholera toxin (CT) is the etiological agent of cholera. Here we report that multiple classes of fucosylated glycoconjugates function in CT binding and intoxication of intestinal epithelial cells. In Colo205 cells, knockout (KO) of B3GNT5, which encodes an enzyme required for synthesis of lacto and neolacto series glycosphingolipids (GSLs), reduces CT binding but sensitizes cells to intoxication. Overexpressing B3GNT5 to generate more fucosylated GSLs confers protection against intoxication, indicating that fucosylated GSLs act as decoy receptors for CT. KO of B3GALT5 causes increased production of fucosylated O-linked and N-linked glycoproteins and leads to increased CT binding and intoxication. KO of B3GNT5 in B3GALT5-KO cells eliminates production of fucosylated GSLs but increases intoxication, identifying fucosylated glycoproteins as functional receptors for CT. These findings provide insight into the molecular determinants regulating CT sensitivity of host cells.

霍乱毒素 （CT） 是霍乱的病原体。在这里，我们报道了多类岩藻糖基化糖缀合物在肠上皮细胞的 CT 结合和中毒中发挥作用。在 Colo205 细胞中，B3GNT5 的敲除 （KO） 编码合成乳糖和新乳系列鞘糖脂 （GSL） 所需的酶，可降低 CT 结合，但使细胞对中毒敏感。过表达 B3GNT5 以产生更多的岩藻糖基化 GSL 可防止中毒，表明岩藻糖基化 GSL 充当 CT 的诱饵受体。B3GALT5 的 KO 导致岩藻糖基化 O-连接和 N-连接糖蛋白的产生增加，并导致 CT 结合和中毒增加。在 B3GALT5-KO 细胞中 B3GNT5 的 KO 消除了岩藻糖基化 GSL 的产生，但增加了中毒，将岩藻糖基化糖蛋白识别为 CT 的功能受体。这些发现为调节宿主细胞 CT 敏感性的分子决定因素提供了见解。