Laboratory of Veterinary Public Health, School of Veterinary Medicine and Animal Sciences, Kitasato University, Higashi 23-35-1, Towada, Aomori, 034-8628, Japan.
Department of Bacterial Infections, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
BMC Microbiol. 2020 Mar 30;20(1):69. doi: 10.1186/s12866-020-01755-1.
Vibrio vulnificus hemolysin (VVH) is a pore-forming toxin secreted by Vibrio vulnificus. Cellular cholesterol was believed to be the receptor for VVH, because cholesterol could bind to VVH and preincubation with cholesterol inhibited cytotoxicity. It has been reported that specific glycans such as N-acetyl-D-galactosamine and N-acetyl-D-lactosamine bind to VVH, however, it has not been known whether these glycans could inhibit the cytotoxicity of VVH without oligomer formation. Thus, to date, binding mechanisms of VVH to cellular membrane, including specific receptors have not been elucidated.
We show here that VVH associates with ganglioside GM1a, Fucosyl-GM1, GD1a, GT1c, and GD1b by glycan array. Among them, GM1a could pulldown VVH. Moreover, the GD1a inhibited the cytotoxicity of VVH without the formation of oligomers.
This is the first report of a molecule able to inhibit the binding of VVH to target cells without oligomerization of VVH.
创伤弧菌溶血素（VVH）是创伤弧菌分泌的一种形成孔的毒素。细胞胆固醇被认为是 VVH 的受体，因为胆固醇可以与 VVH 结合，而胆固醇预孵育则可以抑制细胞毒性。据报道，特定的聚糖，如 N-乙酰-D-半乳糖胺和 N-乙酰-D-乳糖胺，与 VVH 结合，但目前尚不清楚这些聚糖是否可以在不形成寡聚物的情况下抑制 VVH 的细胞毒性。因此，迄今为止，尚未阐明 VVH 与细胞膜结合的机制，包括特定的受体。
我们在这里展示了 VVH 通过聚糖阵列与神经节苷脂 GM1a、岩藻糖基-GM1、GD1a、GT1c 和 GD1b 相关。其中，GM1a 可以拉下 VVH。此外，GD1a 抑制了 VVH 的细胞毒性，而没有形成寡聚物。
这是第一个能够抑制 VVH 与靶细胞结合而不形成 VVH 寡聚物的分子的报告。
