Host-cell specificity and transcytosis of nontoxic nonhemagglutinin protein of botulinum neurotoxin serotype D
Host-cell specificity and transcytosis of nontoxic nonhemagglutinin protein of botulinum neurotoxin serotype D
复制标题
肉毒杆菌神经毒素 D 血清型无毒非血凝素蛋白的宿主细胞特异性和转胞吞作用
DOI：
10.1111/1574-6968.12527
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
and Yoshimasa Sagane
中科院分区：
文献类型：
--
作者：
Shin-Ichiro Miyashita;Koichi Niwa;Toshihiro Watanabe;and Yoshimasa Sagane
D型肉毒杆菌毒素(BoNT)复合体(TC)是动物食源性肉毒中毒的病原体，通过胃肠道和循环，最终定位于神经肌肉接头，在那里D型BoNT裂解参与神经递质释放的底物Synaptobrevin II。在这个过程中，BoNT必须通过细胞，从而从肠腔到达肠道和血管的细胞。肉毒杆菌TC是由BONT与至少一种无毒蛋白结合而成，该无毒蛋白可能是一种无毒的非血凝素(NTNHA)。在这项工作中，我们检测了D型NTNHA蛋白在上皮细胞和内皮细胞中的结合和跨细胞作用，以阐明该蛋白在毒素传递中所起的作用。我们的研究表明，NTNHA与大鼠肠上皮细胞(IEC-6)和牛主动脉内皮细胞(BAEC)结合并跨细胞转运。NTNHA也能与犬肾(MDCK)或人结肠癌(Caco-2)细胞结合，但不能通过MDCK或Caco-2细胞。NTNHA蛋白转胞的这种特异性可以解释为什么只有一些动物对肉毒杆菌毒素敏感。敏感度取决于游戏中的毒素血清型，以及毒素的传递途径。
Serotype D botulinum toxin (BoNT) complex (TC), a causative agent of foodborne botulism in animals, traverses the gastrointestinal tract and circulation, eventually becoming localized in neuromuscular junctions, where the serotype D BoNT cleaves SNARE substrate synaptobrevin II involved in neurotransmitter release. During this process, BoNT must pass through cells, thus from the intestinal lumen to the cells of the intestinal tract and blood vessels. The botulinum TC is formed by association of the BoNT with at least one nontoxic protein, which may be a nontoxic nonhemagglutinin (NTNHA). In this work, we examined the binding and transcytosis of serotype D NTNHA protein in epithelial and endothelial cells to clarify the role played by the protein in toxin delivery. Our studies showed that NTNHA bound to and transcytosed across rat intestinal epithelial (IEC-6) and bovine aortic endothelial (BAEC) cells. While NTNHA also bound to canine renal (MDCK) or human colon carcinoma (Caco-2) cells, but it did not traverse across MDCK or Caco-2 cells. Such specificity of NTNHA protein transcytosis may explain why only some animals are sensitive to botulinum toxin. The sensitivity depends on the toxin serotype in play, and the route of toxin delivery.