RRC ID 19217
Author Niwa K, Yoneyama T, Ito H, Taira M, Chikai T, Kouguchi H, Suzuki T, Hasegawa K, Miyata K, Inui K, Ikeda T, Watanabe T, Ohyama T.
Title Sialic acid-dependent binding and transcytosis of serotype D botulinum neurotoxin and toxin complex in rat intestinal epithelial cells.
Journal Vet Microbiol
Abstract A large toxin complex (L-TC) produced by Clostridium botulinum is composed of neurotoxin (BoNT), non-toxic non-hemagglutinin (NTNHA) and hemagglutinin subcomponents (HA-70, -33 and -17). In animal botulism, BoNT or L-TC is internalized by intestinal epithelial cells. Previous studies showed that L-TC binds to intestinal cells via sugar chains on the cell surface, but the role of toxin binding to sugar chains in the toxin absorption from intestine is unclear. To clarify whether the toxin binding to sugar chains on intestinal cell surface leads to its transcytosis across the cells, we examined binding and permeation of BoNT and L-TC of C. botulinum serotype D strain 4947 to the rat intestinal epithelial cell line IEC-6 in semi-permeable filters in Transwell systems. Both BoNT and L-TC bound to and permeated the cell monolayers, with L-TC showing greater binding and permeation. In addition, both binding and permeation of toxins were potently inhibited by N-acetyl neuraminic acid in the cell culture medium or by treatment of the cells with neuraminidase. However, neither galactose, lactose nor N-acetyl galactosamine inhibited binding or permeation of toxins. These results support the idea that permeation of both BoNT and L-TC through the intestinal cell layer depends on prior binding to sialic acid on the cell surface. This is the first report demonstrating that the binding of botulinum toxins to cell surface sialic acid leads to their transcytosis through intestinal epithelial cells.
Volume 141(3-4)
Pages 312-20
Published 2010-3-24
DOI 10.1016/j.vetmic.2009.09.008
PII S0378-1135(09)00409-X
PMID 19786330
MeSH Animals Botulinum Toxins / metabolism* Carbohydrates / pharmacology Cell Line Epithelial Cells / metabolism* Intestinal Mucosa / cytology Intestinal Mucosa / metabolism N-Acetylneuraminic Acid / metabolism* Neuraminidase / metabolism Permeability / drug effects Protein Binding / drug effects Rats
IF 3.03
Times Cited 15
Human and Animal Cells IEC 6(RCB0993)