Inhibition of Bacterial Adhesion and Toxin Binding by Glycoconjugate and Oligosaccharide Receptor Analogues in Human Milk

Abstract

Following the discovery that the receptor for cholera toxin is a specific glycolipid, the ganglioside GM1 (see Holmgren, 1981), many other toxins and pathogenic bacteria have been found to attach to epithelial receptors being of a carbohydrate nature. Secretions, e.g. human milk, normally contain a variety of glycoproteins, glycolipids, and free oligosaccharides. At least in vitro the attachment of bacteria and toxins to epithelial cells can be completely inhibited by soluble receptor molecules. We assumed that some of the carbohydrate substances in secretions, including human milk, might be structure analogues of cell membrane receptors for bacterial pathogens or their toxins and could thus be able to function as competitive inhibitors. Such receptor analogues, if present in milk, could possibly be involved in the protection against enteric infections and respiratory infections ascribed to breast feeding. We have therefore tested the ability of glycoconjugates and oligosaccharides of human colostrum and milk to inhibit different Vibrio cholerae and enterotoxinogenic Escherichia coli (ETEC) bacteria from adhering to mammalian cells, and their enterotoxins from binding to GM1 receptor ganglioside (Holmgren et al. 1981; 1983). In this paper we will summarize the findings from these earlier studies and provide new, additional information on these systems. We will also briefly review the work by other investigators along the same lines, and discuss the possible significance of the findings.