This Article Full Text Full Text (PDF) Other Versions of this Article: AAC.01009-07v1 52/1/220    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chatterjee, A. Articles by Chowdhury, R. Search for Related Content PubMed PubMed Citation Articles by Chatterjee, A. Articles by Chowdhury, R.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, January 2008, p. 220-224, Vol. 52, No. 1
0066-4804/08/$08.00+0     doi:10.1128/AAC.01009-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Bile and Unsaturated Fatty Acids Inhibit the Binding of Cholera Toxin and Escherichia coli Heat-Labile Enterotoxin to GM1 Receptor

Biophysics Division, Indian Institute of Chemical Biology, Calcutta 700 032, India

Received 1 August 2007/ Returned for modification 28 August 2007/ Accepted 9 October 2007

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 K_d 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.

Published ahead of print on 22 October 2007.