Bile and Unsaturated Fatty Acids Inhibit the Binding of Cholera Toxin and Escherichia coli Heat-Labile Enterotoxin to GM1 Receptor
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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Title |
Bile and Unsaturated Fatty Acids Inhibit the Binding of Cholera Toxin and Escherichia coli Heat-Labile Enterotoxin to GM1 Receptor
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Creator |
Chatterjee, Arpita
Chowdhury, Rukhsana |
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Subject |
Infectious Diseases and Immunology
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Description |
Cholera toxin (CT) is an archetypal bacterial toxin that binds with a high affinity to the receptor ganglioside
GM1 on the intestinal epithelial surface and that causes the severe watery diarrhea characteristic of the
disease cholera. Blockage of the interaction of CT with the GM1 receptor is an attractive approach for
therapeutic intervention. We report here that crude bile prevents the interaction of CT with GM1 and reduces
CT-mediated fluid accumulation in the rabbit intestine. The unsaturated fatty acids detected in crude bile,
arachidonic, linoleic, and oleic acids, were found to be the most effective. Crude bile and the unsaturated fatty
acids interacted with CT but not GM1 to prevent CT-GM1 binding. Neither crude bile nor the unsaturated fatty
acids had any effect on the subunit structure of CT. The binding of CT to unsaturated fatty acids resulted in
a shift of the apparent pI of CT from 6.8 to 8.2 and a marked decrease in intrinsic fluorescence. The Kd was
calculated from fluorescence quenching assays. It was demonstrated by the rabbit ileal loop model that
practically no fluid accumulated in the intestinal loops when CT was administered together with inhibitory
concentrations of linoleic acid. The bile present in the intestine was sufficient to inhibit the activity of up to 300
ng CT. Bile and unsaturated fatty acids also inhibited the binding of Escherichia coli heat-labile enterotoxin
(LT) to GM1, and no fluid accumulation was observed in rabbit ileal loops when LT was administered together
with linoleic acid.
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Date |
2008
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Type |
Article
PeerReviewed |
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Format |
application/pdf
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Identifier |
http://www.eprints.iicb.res.in/281/1/ANTIMICROBIAL_AGENTS_AND_CHEMOTHERAPY%2C52(_1)%2C220%2D224_%2C2008[146].pdf
Chatterjee, Arpita and Chowdhury, Rukhsana (2008) Bile and Unsaturated Fatty Acids Inhibit the Binding of Cholera Toxin and Escherichia coli Heat-Labile Enterotoxin to GM1 Receptor. Antimicrobial Agents and Chemotherapy, 52 (1). pp. 220-224. |
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Relation |
http://dx.doi.org/doi:10.1128/AAC.01009-07
http://www.eprints.iicb.res.in/281/ |
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