Copyright © 1991, American Society for Microbiology Toxin A of Clostridium difficile Binds to the Human

Clostridium difficile causes pseudomembranous colitis in humans. The enterotoxin (i.e., toxin A) from this organism is believed to be responsible for the initial intestinal pathology associated with this disease. Previous work shows that this toxin binds to carbohydrates that contain Galal-3GalI01-4GlcNAc. However, this carbohydrate is not present on normal human cells. Therefore, this study was undertaken to identify potential receptors for toxin A that do exist on human intestinal epithelium. Using enzyme-linked immunosorbent assay, affinity chromatography, and altered migration in an electric field, we assayed the binding of toxin A to purified carbohydrates and glycoproteins. We found that toxin A bound to the carbohydrate antigens designated I, X, and Y. Each of these carbohydrates exist on the intestinal epithelium of humans. Clostridium difficile is one of the most common causes of bacterial diarrhea and colitis among hospitalized patients. The organism cannot compete successfully with the normal microflora of the adult colon but can grow to high numbers when the colonic flora has been disturbed by antibiotic treatments (35, 45). C. difficile then keeps the colonic flora from reestablishing itself by producing an enterotoxin, toxin A, which causes destruction of the colonic epithelium, resulting in fluid secretion into the intestine (25, 27). A second toxin produced by C. difficile, toxin B, has no effect on undisturbed intestinal epithelium but is an extremel