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Research Article Free access | 10.1172/JCI118835

Rabbit sucrase-isomaltase contains a functional intestinal receptor for Clostridium difficile toxin A.

C Pothoulakis, R J Gilbert, C Cladaras, I Castagliuolo, G Semenza, Y Hitti, J S Montcrief, J Linevsky, C P Kelly, S Nikulasson, H P Desai, T D Wilkins, and J T LaMont

Section of Gastroenterology, Boston University School of Medicine, Massachusetts, USA.

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Section of Gastroenterology, Boston University School of Medicine, Massachusetts, USA.

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Section of Gastroenterology, Boston University School of Medicine, Massachusetts, USA.

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Section of Gastroenterology, Boston University School of Medicine, Massachusetts, USA.

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Section of Gastroenterology, Boston University School of Medicine, Massachusetts, USA.

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Section of Gastroenterology, Boston University School of Medicine, Massachusetts, USA.

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Section of Gastroenterology, Boston University School of Medicine, Massachusetts, USA.

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Section of Gastroenterology, Boston University School of Medicine, Massachusetts, USA.

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Section of Gastroenterology, Boston University School of Medicine, Massachusetts, USA.

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Section of Gastroenterology, Boston University School of Medicine, Massachusetts, USA.

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Section of Gastroenterology, Boston University School of Medicine, Massachusetts, USA.

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Section of Gastroenterology, Boston University School of Medicine, Massachusetts, USA.

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Published August 1, 1996 - More info

Published in Volume 98, Issue 3 on August 1, 1996
J Clin Invest. 1996;98(3):641–649. https://doi.org/10.1172/JCI118835.
© 1996 The American Society for Clinical Investigation
Published August 1, 1996 - Version history
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Abstract

The intestinal effects of Clostridium difficile toxin A are inidated by toxin binding to luminal enterocyte receptors. We reported previously that the rabbit ileal brush border (BB) receptor is a glycoprotein with an alpha-d-galactose containing trisaccharide in the toxin-binding domain (1991. J. Clin. Invest. 88:119-125). In this study we characterized the rabbit ileal BB receptor for this toxin. Purified toxin receptor peptides of 19 and 24 amino acids showed 100% homology with rabbit sucrase-isomaltase (SI). Guinea pig receptor antiserum reacted in Western blots with rabbit SI and with the purified toxin receptor. Antireceptor IgG blocked in vitro binding of toxin A to rabbit ileal villus cell BB. Furthermore, anti-SI IgG inhibited toxin A-induced secretion (by 78.1%, P < 0.01), intestinal permeability (by 80.8%, P < 0.01), and histologic injury (P < 0.01) in rabbit ileal loops in vivo. Chinese hamster ovary cells transfected with SI cDNA showed increased intracellular calcium increase in response to native toxin (holotoxin) or to a recombinant 873-amino acid peptide representing the receptor binding domain of toxin A. These data suggest that toxin A binds specifically to carbohydrate domains on rabbit ileal SI, and that such binding is relevant to signal transduction mechanisms that mediate in vitro and in vivo toxicity.

Version history
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