Karl-Anders Karlsson

Carbohydrate Binding Specificity of the Neutrophil-activating Protein of Helicobacter pylori

The possible interaction of the neutrophil-activating protein of Helicobacter pylori with target cell glycoconjugates was investigated by the binding of125I-labeled recombinant protein to glycosphingolipids from human neutrophils in solid phase assays. Thereby, a distinct binding of the neutrophil-activating protein to four bands in the acid glycosphingolipid fraction from human neutrophils was detected, whereas no binding to the non-acid glycosphingolipids or polyglycosyl ceramides from these cells was obtained. When using glycosphingolipids not present in the cell membrane of human neutrophils, it was found that the neutrophil-activating protein also bound to sulfated glycosphingolipids as sulfatide and sulfated gangliotetraosyl ceramide. Comparison of the binding preferences of the protein to reference glycosphingolipids from other sources suggested that in human granulocytes, the neutrophil-activating protein of H. pylori preferentially recognizes glycoconjugates with a terminally unsubstituted NeuAcα3Galβ4GlcNAcβ3Galβ4GlcNAcβ sequence.

Membrane Proximity and Internal Binding in the Microbial Recognition of Host Cell Glycolipids: A Conceptual Discussion

Carbohydrates are important receptor substances on animal cells for the attachment of various microbes. The distinct development during the last few years of assay, separation and structural techniques for glycoconjugates, in combination with improved information in microbial molecular biology, is at present contributing with information on receptor characteristics that holds promise also for drug design.1 The most spectacular example in the microbial area is the crystal conformation of the complex of influenza virus hemagglutinin with its receptor, N-acetylneuraminic acid or sialic acid,2 allowing considerations at an atomic level.

Characteristics of the Recognition of Host Cell Carbohydrates by Viruses and Bacteria

Microbial interactions with host tissues is at present a field in a fascinating development both basically and concerning potential applications. Our knowledge of virus receptors is more advanced than that of bacterial systems, in part based on the crystal conformation of the influenza virus hemagglutinin in complex with the receptor, sialic acid (1), and the crystal structures of picornaviruses (see 2). The “Canyon hypothesis” (2) suggests that one strategy for viruses to escape immune surveillance is to protect the receptor attachment site in a surface depression which is too narrow to be reached by antibodies. This site is conserved on the otherwise hypervariable surface of the viruses. Development of protective vaccines may therefore get very difficult or impossible, and efforts are growing to prepare soluble receptor analogues that may inhibit viral attachment, based on carbohydrate (1,3,4) or protein (2,5,6) receptors, and there appears to be good opportunities for rational drug design.