THE USE OF LIPID-LINKED OLIGOSACCHARIDES (NEOGLYCOLIPIDS) IN THE IDENTIFICATION OF CARBOHYDRATE RECEPTORS FOR MICROBIAL PATHOGENS

Specific oligosaccharide chains on the host cell surface act as recept ors for many microbial pathogens. Identification of receptor structure s is an important step in the understanding of the pathogenesis of inf ection. Glycolipid receptors have been identified by direct binding as says. However, technical difficulties have prevented demonstration of bacterial binding to the oligosaccharides of glycoproteins; these have been identified mainly by inhibition assays. By a novel technique dev eloped in our laboratory, oligosaccharides released from glycoproteins are linked to lipids to form neoglycolipids. These can be used in bac terial binding assays. The feasibility of this approach has been demon strated using type 1 fimbriated Escherichia coli binding specifically to neoglycolipids rich in mannose residues. The application of the met hod has resulted in a demonstration of a new type of adhesive specific ity for E coli and differences in the binding specificities of E coli and Pseudomonas aeruginosa. Further application of this technique by g enerating oligosaccharides purified from mucus glycoproteins from pati ents with cystic fibrosis to use in binding assays with P aeruginosa i s currently being undertaken. The basic knowledge gained by this appro ach may in time see the development of novel therapy in the form of re ceptor blocking agents.