Abstract
Fimbriae are long, proteinaceous adhesion organelles expressed on the bacterial envelope, evolutionarily adapted by Escherichia coli strains for the colonization of epithelial linings. Using glycan arrays of the Consortium for Functional Glycomics (CFG), the lectin domains were screened of the fimbrial adhesins F17G and FedF from enterotoxigenic E. coli (ETEC) and of the FimH adhesin from uropathogenic E. coli. This has led to the discovery of a more specific receptor for F17G, GlcNAcβ1,3Gal. No significant differences emerged from the glycan binding profiles of the F17G lectin domains from five different E. coli strains. However, strain-dependent amino acid variations, predominantly towards the positively charged arginine, were indicated by sulfate binding in FedF and F17G crystal structures. For FedF, no significant binders could be observed on the CFG glycan array. Hence, a shotgun array was generated from microvilli scrapings of the distal jejunum of a 3-week old piglet about to be weaned. On this array, the blood group A type 1 hexasaccharide emerged as a receptor for the FedF lectin domain and remarkably also for F18-fimbriated E. coli. F17G was found to selectively recognize glycan species with a terminal GlcNAc, typifying intestinal mucins. In conclusion, F17G and FedF recognize long glycan sequences that could only be identified using the shotgun approach. Interestingly, ETEC strains display a large capacity to adapt their fimbrial adhesins to ecological niches via charge-driven interactions, congruent with binding to thick mucosal surfaces displaying an acidic gradient along the intestinal tract.
Highlights
Bacterial adhesion to mammalian tissue constitutes the first step in host colonization, through specific structures known as fimbriae and pili
Amino acid sequence and crystal structure analyses of the lectin domains of F17G, FedF and FimH elucidate a previously unacknowledged basis for strain-dependent glycan binding profiles of E. coli fimbrial adhesins, one that is driven by electrostatic interactions
All five F17G variant receptor binding domains (a, b, d, e, f), FedF, and FimH, were screened on pre-designed glycan arrays displaying natural N-linked glycans as well as on the shotgun microarrays designed from F18-fimbriated E. coli target tissues
Summary
Bacterial adhesion to mammalian tissue constitutes the first step in host colonization, through specific structures known as fimbriae and pili. Clinical strains of F17G display amino acid sequence variation of up to 10% and six natural variants (termed a±f) of the F17 operon have been previously identified [6,14,15]. The specificity profiles of the lectin domains of five of the F17G variants, one FedF variant A crystal structure of the F17G lectin domain, variant b, in complex with GlcNAcE1,3Gal, has been refined to high-resolution. F17G crystal structures in complex with these disaccharides provide insight in the structural basis of the variant-specific binding profiles. Amino acid sequence and crystal structure analyses of the lectin domains of F17G, FedF and FimH elucidate a previously unacknowledged basis for strain-dependent glycan binding profiles of E. coli fimbrial adhesins, one that is driven by electrostatic interactions
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