Rabbit Sucrase-Isomaltase Contains a Functional Intestinal Receptor for Clostridium difficile Toxin A.
Pothoulakis, Charalabos; Gilbert, Richard J. **; Cladaras, Christos; Castagliuolo, Ignazio; Semenza, Giorgio *****; Hitti, Yousef; Montcrief, J. Scott ***; Linevsky, Joanne; Kelly, Ciaran P.; Nikulasson, Sigfus *; Desai, Himanshu P. ****; Wilkins, Tracy D. ***; LaMont, J. Thomas
[Article] Journal of Clinical Investigation. 98(3):641-649, August 1, 1996.

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The intestinal effects of Clostridium difficile toxin A are initiated 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. (J. Clin. Invest. 1996. 98:641-649.)

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