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 receptors for many microbial pathogens. Identification of receptor structures is an important step in the understanding of the pathogenesis of infection. Glycolipid receptors have been identified by direct binding assays. 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 developed in our laboratory, oligosaccharides released from glycoproteins are linked to lipids to form neoglycolipids. These can be used in bacterial binding assays. The feasibility of this approach has been demonstrated using type 1 fimbriated Escherichia coli binding specifically to neoglycolipids rich in mannose residues. The application of the method has resulted in a demonstration of a new type of adhesive specificity for E. coli and differences in the binding specificities of E coli and Pseudomonas aeruginosa. Further application of this technique by generating oligosaccharides purified from mucus glycoproteins from patients with cystic fibrosis to use in binding assays with P aeruginosa is currently being undertaken. The basic knowledge gained by this approach may in time see the development of novel therapy in the form of receptor blocking agents.
Glycoconjugates Section, MRC Clinical Research Centre, Harrow, Middlesex, UK.
I J
IJ
Rosenstein
D001419:Bacteria / Q000472:pathogenicity*; D001422:Bacterial Adhesion; D001431:Bacteriological Techniques; D050260:Carbohydrate Metabolism; D004926:Escherichia coli / Q000472:pathogenicity; D006017:Glycolipids / Q000378:metabolism; D066298:In Vitro Techniques; D009844:Oligosaccharides / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity; D011956:Receptors, Cell Surface / Q000032:analysis*
D006017:Glycolipids; D009844:Oligosaccharides; D011956:Receptors, Cell Surface