Valency conversion in the type 1 fimbrial adhesin of Escherichia coli

FimH protein is a lectin-like adhesive subunit of type 1, or mannose-sensit ive, fimbriae that are found on the surface of most Escherichia coli strain s. All naturally occurring FimH variants demonstrate a conserved mannotrios e-specific (i.e. multivalent) binding. Here, we demonstrate that replacemen t of residues 185-279 within the FimH pilin domain with a corresponding seg ment of the type 1C fimbrial adhesin FocH leads to a loss of the multivalen t mannotriose-specific binding property accompanied by the acquisition of a distinct monomannose-specific (i.e. monovalent) binding capability. Bacter ia expressing the monovalent hybrid adhesins were capable of binding strong ly to uroepithelial tissue culture cells and guinea pig erythrocytes. They could not, however, agglutinate yeast or bind human buccal cells functions readily accomplished by the E. coli-expressing mannotriose-specific FimH va riants. Based on the relative potency of inhibiting compounds of different structures, the receptor binding site within monovalent FimH-FocH adhesin h as an extended structure with an overall configuration similar to that with in the multivalent FimH of natural origin. The monomannose-only specific ph enotype could also be invoked by a single point mutation, E89K, located wit hin the lectin domain of FimH, but distant from the receptor binding site. The structural alterations influence the receptor-binding valency of the Fi mH adhesin via distal effects on the combining pocket, obviously by affecti ng the FimH quaternary structure.