Effect of inhibitors on glycoprotein biosynthesis and bacterial adhesion.

Group B streptococci adhere to influenza-virus infected canine kidney epithelial cells but not to uninfected cells. For studies of the molecular nature of this interaction the bacteria were radiolabelled and a quantitative binding assay was developed with which the following properties of the system were observed. (1) Adhesion was specific for group B streptococci (GBS); streptococci from other serological groups did not bind and did not inhibit adhesion of radioactive GBS. (2) Binding of GBS to infected kidney cells was inhibited by the addition of cell walls from GBS to the kidney cell monolayers. (3) Preincubation of GBS with free influenza virus prevented their attachment to infected kidney cell monolayers. With a centrifugation type of assay, labelled influenza virus bound to GBS. This binding could be inhibited by several glycoproteins after removal of the terminal sialic acid. Asialo-glycopeptides of the complex type, isolated from these inhibitory glycoproteins, also bound to GBS. The influenza viral glycoproteins have been partially characterized and shown to contain a glycosylamine type of complex oligosaccharide. This type of oligosaccharide is biosynthesized by means of lipid-linked saccharide intermediates. Several antibiotics such as tunicamycin and streptovirudin, and other inhibitors such as 2-deoxyglucose and glucosamine, inhibit this lipid-linked pathway. These inhibitors also prevent the formation of mature influenza virus as well as the adherence of group B streptococci. Other inhibitors of protein glycosylation should be valuable as tools for improving further our understanding of the mechanism of cell adhesion.