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The verotoxin (Shiga toxin) of Shiga toxin producing organisms—such as Escherichia coli0157:H7, binds to specific carbohydrate containing receptors on intestinal epithelial cells and on renal and vascular endothelial cells. Treatment aimed at preventing this binding should be effective. Work in California (Adrienne W Paton et al. Nature Medicine2000;6:265–70; see also commentaryIbid: 257–8) may have made this possible.
Theoretically, the enterotoxin could be bound by administering synthetic carbohydrate which mimics the natural enterotoxin receptor, but the problem with this approach is that such synthetic carbohydrate binds only small amounts of enterotoxin and very large doses would be needed. The Californian workers have apparently overcome this difficulty in an ingenious way. They took a strain ofE coli which lacked the enzymes responsible for lipopolysaccharide production (glycosyl transferases) and inserted into it two new galactosyl transferase genes, one from a meningococcus and one from a gonococcus. The E coli then produced lots of lipopolysaccharide with the same end units as the enterotoxin receptor. The dried bacteria were 10 000 times more effective at binding enterotoxin than was the synthetic carbohydrate previously available, and a live or dead preparation of the transformedE coli given orally to mice protected them against a lethal dose of verotoxin.
Another recent report, inNature (PI Kitov et al. 2000;403:669–72) described the stereochemical synthesis of a complex trisaccharide containing molecule (called STARFISH because of its configuration) with high affinity for verotoxin. It is suggested that oral administration of the bacterial preparation might bind verotoxin in the gut and intravenous administration of the STARFISH complex might deal with systemic verotoxin.
The hope, of course, is that these new preparations can be given at the right time and in sufficient quantity to influence the course or development of the haemolytic uraemic syndrome.