Fucosylated Molecules Competitively Interfere with
Cholera Toxin Binding to Host Cells
Version 2 2018-02-22, 20:05
Version 1 2018-02-22, 15:49
Posted on 2018-02-22 - 20:05
Cholera toxin (CT) enters host intestinal
epithelia cells, and
its retrograde transport to the cytosol results in the massive loss
of fluids and electrolytes associated with severe dehydration. To
initiate this intoxication process, the B subunit of CT (CTB) first
binds to a cell surface receptor displayed on the apical surface of
the intestinal epithelia. While the monosialoganglioside GM1 is widely
accepted to be the sole receptor for CT, intestinal epithelial cell
lines also utilize fucosylated glycan epitopes on glycoproteins to
facilitate cell surface binding and endocytic uptake of the toxin.
Further, l-fucose can competively inhibit CTB binding to
intestinal epithelia cells. Here, we use competition binding assays
with l-fucose analogs to decipher the molecular determinants
for l-fucose inhibition of cholera toxin subunit B (CTB)
binding. Additionally, we find that mono- and difucosylated oligosaccharides
are more potent inhibitors than l-fucose alone, with the
LeY tetrasaccharide emerging as the most potent inhibitor of CTB binding
to two colonic epithelial cell lines (T84 and Colo205). Finally, a
non-natural fucose-containing polymer inhibits CTB binding two orders
of magnitude more potently than the LeY glycan when tested against
Colo205 cells. This same polymer also inhibits CTB binding to T84
cells and primary human jejunal epithelial cells in a dose-dependent
manner. These findings suggest the possibility that polymeric display
of fucose might be exploited as a prophylactic or therapeutic approach
to block the action of CT toward the human intestinal epithelium.
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Wands, Amberlyn
M.; Cervin, Jakob; Huang, He; Zhang, Ye; Youn, Gyusaang; Brautigam, Chad A.; et al. (2018). Fucosylated Molecules Competitively Interfere with
Cholera Toxin Binding to Host Cells. ACS Publications. Collection. https://doi.org/10.1021/acsinfecdis.7b00085
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AUTHORS (15)
AW
Amberlyn
M. Wands
JC
Jakob Cervin
HH
He Huang
YZ
Ye Zhang
GY
Gyusaang Youn
CB
Chad A. Brautigam
MD
Maria Matson Dzebo
PB
Per Björklund
VW
Ville Wallenius
DB
Danielle K. Bright
CB
Clay S. Bennett
PW
Pernilla Wittung-Stafshede
NS
Nicole S. Sampson
UY
Ulf Yrlid
JK
Jennifer J. Kohler
KEYWORDS
monosialoganglioside GM 1T 84 cellscell surface bindingjejunal epithelial cellsCTB bindingColo 205 cellsfucosylated glycan epitopescell surface receptorHost Cells Cholera toxinepithelia cellsFucosylated Molecules Competitively Interferenon-natural fucose-containing polymercholera toxin subunit Bepithelial cell linesuse competition binding assaysCholera Toxin Bindingl-fucose