Quantitative studies of the binding of the class II PapG adhesin from uropathogenic Escherichia coli to oligosaccharides.
Binding of the class II PapG adhesin, found at the tip of filamentous pili on Escherichia coli, to the carbohydrate moiety of globoseries glycolipids in the human kidney is a key step in development of pyelonephritis, a severe form of urinary tract infection. An assay based on surface plasmon resonance for quantification of the binding of the class II PapG adhesin to oligosaccharides has been developed. Using this assay dissociation constants ranging from 80 to 540 microM were determined for binding of the PapG adhesin to di-pentasaccharide fragments from the globoseries of glycolipids. A series of galabiose derivatives, modified at the anomeric position, O-2' or O-3', was also investigated. The anomeric position appeared to be the most promising for development of improved inhibitors of PapG-mediated adhesion of E. coli. p-Methoxyphenyl galabioside was found to be most potent (K(d)=140 microM), and binds to PapG almost as well as the Forssman pentasaccharide.
Larsson
Andreas
A
Organic Chemistry, Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden.
Ohlsson
Jörgen
J
Dodson
Karen W
KW
Hultgren
Scott J
SJ
Nilsson
Ulf
U
Kihlberg
Jan
J
D018830:Adhesins, Escherichia coli / Q000737:chemistry* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects*; D001665:Binding Sites; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D004187:Disaccharides / Q000737:chemistry; D004927:Escherichia coli Infections / Q000382:microbiology; D036781:Fimbriae Proteins / Q000737:chemistry* / Q000378:metabolism; D005577:Forssman Antigen; D005697:Galactosides / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism; D020349:Surface Plasmon Resonance; D014552:Urinary Tract Infections / Q000382:microbiology
D018830:Adhesins, Escherichia coli; D000900:Anti-Bacterial Agents; D004187:Disaccharides; C402893:Forssman pentasaccharide; D005697:Galactosides; D009844:Oligosaccharides; C092426:PapG protein, E coli; D011956:Receptors, Cell Surface; C032103:4-O-alpha-D-galactopyranosyl-D-galactose; D036781:Fimbriae Proteins; D005577:Forssman Antigen