Miyashita Shin-Ichiro, Sagane Yoshimasa, Suzuki Tomonori, Matsumoto Takashi, Niwa Koichi, Watanabe Toshihiro
Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493, Japan.
Department of Nutritional Science and Food Safety, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.
Sci Rep. 2016 Aug 10;6:31043. doi: 10.1038/srep31043.
The botulinum neurotoxin (BoNT) causes muscle paralysis and is the most potent toxin in nature. BoNT is associated with a complex of auxiliary "Non-Toxic" proteins, which constitute a large-sized toxin complex (L-TC). However, here we report that the "Non-Toxic" complex of serotype D botulinum L-TC, when administered to rats, exerts in-vivo toxicity on small-intestinal villi. Moreover, Serotype C and D of the "Non-Toxic" complex, but not BoNT, induced vacuole-formation in a rat intestinal epithelial cell line (IEC-6), resulting in cell death. Our results suggest that the vacuole was formed in a manner distinct from the mechanism by which Helicobacter pylori vacuolating toxin (VacA) and Vibrio cholerae haemolysin induce vacuolation. We therefore hypothesise that the serotype C and D botulinum toxin complex is a functional hybrid of the neurotoxin and vacuolating toxin (VT) which arose from horizontal gene transfer from an ancestral BoNT-producing bacterium to a hypothetical VT-producing bacterium.
肉毒杆菌神经毒素（BoNT）可导致肌肉麻痹，是自然界中最具毒性的毒素。BoNT与一组辅助性“无毒”蛋白相关联，这些蛋白构成了一个大型毒素复合物（L-TC）。然而，我们在此报告，D型肉毒杆菌L-TC的“无毒”复合物在给大鼠施用时，会对小肠绒毛产生体内毒性。此外，“无毒”复合物的C型和D型（而非BoNT）在大鼠肠上皮细胞系（IEC-6）中诱导液泡形成，导致细胞死亡。我们的结果表明，液泡形成的方式与幽门螺杆菌空泡毒素（VacA）和霍乱弧菌溶血素诱导空泡形成的机制不同。因此，我们推测C型和D型肉毒杆菌毒素复合物是神经毒素和空泡毒素（VT）的功能性杂种，它是通过水平基因转移从产生BoNT的祖先细菌转移到假想的产生VT的细菌而产生的。
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