The affinity of the FimH fimbrial adhesin is receptor-driven and quasi-independent of Escherichia coli pathotypes

Mol Microbiol. 2006 Sep;61(6):1556-68. doi: 10.1111/j.1365-2958.2006.05352.x. Epub 2006 Aug 23.

Abstract

Type-1 fimbriae are important virulence factors for the establishment of Escherichia coli urinary tract infections. Bacterial adhesion to the high-mannosylated uroplakin Ia glycoprotein receptors of bladder epithelium is mediated by the FimH adhesin. Previous studies have attributed differences in mannose-sensitive adhesion phenotypes between faecal and uropathogenic E. coli to sequence variation in the FimH receptor-binding domain. We find that FimH variants from uropathogenic, faecal and enterohaemorrhagic isolates express the same specificities and affinities for high-mannose structures. The only exceptions are FimHs from O157 strains that carry a mutation (Asn135Lys) in the mannose-binding pocket that abolishes all binding. A high-mannose microarray shows that all substructures are bound by FimH and that the largest oligomannose is not necessarily the best binder. Affinity measurements demonstrate a strong preference towards oligomannosides exposing Manalpha1-3Man at their non-reducing end. Binding is further enhanced by the beta1-4-linkage to GlcNAc, where binding is 100-fold better than that of alpha-d-mannose. Manalpha1-3Manbeta1-4GlcNAc, a major oligosaccharide present in the urine of alpha-mannosidosis patients, thus constitutes a well-defined FimH epitope. Differences in affinities for high-mannose structures are at least 10-fold larger than differences in numbers of adherent bacteria between faecal and uropathogenic strains. Our results imply that the carbohydrate expression profile of targeted host tissues and of natural inhibitors in urine, such as Tamm-Horsfall protein, are stronger determinants of adhesion than FimH variation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Escherichia coli / chemistry
  • Adhesins, Escherichia coli / genetics
  • Adhesins, Escherichia coli / metabolism*
  • Amino Acid Sequence
  • Bacterial Adhesion
  • Carbohydrate Sequence
  • Escherichia coli / metabolism
  • Escherichia coli / pathogenicity*
  • Fimbriae Proteins / chemistry
  • Fimbriae Proteins / genetics
  • Fimbriae Proteins / metabolism*
  • Fimbriae, Bacterial / chemistry
  • Fimbriae, Bacterial / metabolism*
  • Hemagglutination
  • Mannose / chemistry
  • Mannose / metabolism
  • Mannosides / chemistry
  • Mannosides / metabolism*
  • Microarray Analysis
  • Molecular Sequence Data
  • Mutation
  • Protein Conformation

Substances

  • Adhesins, Escherichia coli
  • Mannosides
  • fimH protein, E coli
  • Fimbriae Proteins
  • Mannose