title: "Non-Toxic" Proteins of the Botulinum Toxin Complex Exert In-vivo Toxicity.
abstract: 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.
authors: Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493, Japan.
authors: Shin-Ichiro
authors: S
authors: Miyashita
authors: Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493, Japan.
authors: Yoshimasa
authors: Y
authors: Sagane
authors: 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.
authors: Tomonori
authors: T
authors: Suzuki
authors: Rigaku Corporation, 3-9-12 Matsubara-Cho, Akishima 196-8666, Japan.
authors: Takashi
authors: T
authors: Matsumoto
authors: Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493, Japan.
authors: Koichi
authors: K
authors: Niwa
authors: Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493, Japan.
authors: Toshihiro
authors: T
authors: Watanabe
mesh_terms: D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000633:toxicity; D001905:Botulinum Toxins / Q000633:toxicity*; D002460:Cell Line; D003014:Clostridium botulinum / Q000502:physiology*; D016480:Helicobacter pylori / Q000502:physiology; D006459:Hemolysin Factors / Q000633:toxicity; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000648:ultrastructure; D046912:Multiprotein Complexes; D051381:Rats; D014617:Vacuoles / Q000648:ultrastructure*; D014734:Vibrio cholerae / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D046912:Multiprotein Complexes; C074689:VacA protein, Helicobacter pylori; C096325:botulinum toxin type D; D001905:Botulinum Toxins; C096324:botulinum toxin type C