Functional flexibility of the FimH adhesin: Insights from a random mutant library

Schembri, Mark A., Sokurenko, Evgeni V. and Klemm, Per (2000) Functional flexibility of the FimH adhesin: Insights from a random mutant library. Infection and Immunity, 68 5: 2638-2646. doi:10.1128/IAI.68.5.2638-2646.2000

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Author Schembri, Mark A.
Sokurenko, Evgeni V.
Klemm, Per
Title Functional flexibility of the FimH adhesin: Insights from a random mutant library
Journal name Infection and Immunity
ISSN 1098-5522
Publication date 2000-05
Sub-type Article (original research)
DOI 10.1128/IAI.68.5.2638-2646.2000
Open Access Status File (Publisher version)
Volume 68
Issue 5
Start page 2638
End page 2646
Total pages 9
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Abstract Type 1 fimbriae are surface organelles of Escherichia coli which mediate D-mannose-sensitive binding to different host surfaces. This binding is conferred by the minor fimbrial component FimH. Naturally occurring variants of the FimH protein have been selected in nature for their ability to recognize specific receptor targets. In particular, variants that bind strongly to terminally exposed monomannose residues have been associated with a pathogenicity-adaptive phenotype that enhances E. coli colonization of extraintestinal locations such as the urinary bladder. In this study we have used random mutagenesis to specifically identify nonselective mutations in the FimH adhesin which modify its binding phenotype. Isogenic E. coli clones expressing FimH variants were tested for their ability to bind yeast cells and model glycoproteins that contain oligosaccharide moieties rich in either terminal monomannose, oligomannose, or nonmannose residues. Both the monomannose- and the oligomannose-binding capacity of type 1 fimbriae could be altered by minor amino acid changes in the FimH protein. The monomannose- binding phenotype was particularly sensitive to changes, with extensive differences in binding being observed in comparison to wild-type FimH levels. Different structural alterations were able to cause similar functional changes in FimH, suggesting a high degree of flexibility to target recognition by this adhesin. Alteration of residue P49 of the mature FimH protein, which occurs within the recently elucidated carbohydrate-binding pocket of FimH, completely abolished its function. Amino acid changes that increased the binding capacity of FimH were located outside receptor- interacting residues, indicating that functional changes relevant to pathogenicity are likely to be due to conformational changes of the adhesin.
Keyword Fimbriae
Escherichia coli
FimH adhesin
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
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