RRC ID 19254
Author Jin Y, Takegahara Y, Sugawara Y, Matsumura T, Fujinaga Y.
Title Disruption of the epithelial barrier by botulinum haemagglutinin (HA) proteins - differences in cell tropism and the mechanism of action between HA proteins of types A or B, and HA proteins of type C.
Journal Microbiology (Reading)
Abstract Orally ingested botulinum neurotoxin (BoNT) causes food-borne botulism, but BoNT must pass through the gut lining and enter the bloodstream. We have previously found that type B haemagglutinin (HA) proteins in the toxin complex play an important role in the intestinal absorption of BoNT by disrupting the paracellular barrier of the intestinal epithelium, and therefore facilitating the transepithelial delivery of BoNT. Here, we show that type A HA proteins in the toxin complex have a similar disruptive activity and a greater potency than type B HA proteins in the human intestinal epithelial cell lines Caco-2 and T84 and in the canine kidney epithelial cell line MDCK I. In contrast, type C HA proteins in the toxin complex (up to 300 nM) have no detectable effect on the paracellular barrier in these human cell lines, but do show a barrier-disrupting activity and potent cytotoxicity in MDCK I. These findings may indicate that type A and B HA proteins contribute to the development of food-borne botulism, at least in humans, by facilitating the intestinal transepithelial delivery of BoNTs, and that the relative inability of type C HA proteins to disrupt the paracellular barrier of the human intestinal epithelium is one of the reasons for the relative absence of food-borne human botulism caused by type C BoNT.
Volume 155(Pt 1)
Pages 35-45
Published 2009-1-1
DOI 10.1099/mic.0.021246-0
PMID 19118344
MeSH Animals Biological Transport Botulinum Toxins / chemistry* Botulinum Toxins / classification Botulinum Toxins / metabolism Botulinum Toxins, Type A / chemistry Botulinum Toxins, Type A / metabolism Caco-2 Cells Cell Line, Tumor Dogs Electric Impedance Epithelial Cells / drug effects* Hemagglutinins / chemistry Hemagglutinins / metabolism Hemagglutinins / pharmacology* Humans Intestines / cytology* Kidney / cytology*
IF 2.138
Times Cited 54
WOS Category MICROBIOLOGY
Resource
Human and Animal Cells ACL-15(RCB0510) RCN-9(RCB0511)