Structural requirements for the glycolipid receptor of human uropathogenic Escherichia coli.
The binding of uropathogenic Escherichia coli to the globo series of glycolipids via P pili is a critical step in the infectious process that is mediated by a human-specific PapG adhesin. Three classes of PapG adhesins exist with different binding specificities to Gal alpha 4Gal-containing glycolipids. The structural basis for PapG recognition of the human glycolipid receptor globoside was investigated by using soluble saccharide analogues as inhibitors of bacterial haemagglutination. The minimum binding epitope was confirmed as the Gal alpha 4Gal moiety, but parts of the GalNAc beta and glucose residues, which flank the Gal alpha 4Gal in globoside (GbO4), were also shown to be important for strong binding. Furthermore, the same five hydroxyl groups of Gal alpha 4Gal in globotriasyl ceramide that were recognized by a previously characterized PapG variant were also recognized by the human-specific PapG in binding the GbO4 that dominates in the human kidney. Saccharide analogues that blocked haemagglutination also blocked the adherence of human uropathogenic E. coli to human kidney sections. Knowledge of the molecular details of the PapG-GbO4 interaction will make it possible to design antiadherence therapeutics.
D018830:Adhesins, Escherichia coli / Q000378:metabolism*; D001665:Binding Sites; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D004926:Escherichia coli / Q000378:metabolism* / Q000472:pathogenicity; D036781:Fimbriae Proteins; D010861:Fimbriae, Bacterial / Q000502:physiology; D006384:Hemagglutination; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism*; D014552:Urinary Tract Infections / Q000382:microbiology
D018830:Adhesins, Escherichia coli; D009844:Oligosaccharides; C092426:PapG protein, E coli; D011956:Receptors, Cell Surface; C033639:glycolipid receptor; D036781:Fimbriae Proteins