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Structural and Functional Characterization of an F17‐Like CUP Adhesin from Uropathogenic E. coli Isolate UTI89
Author(s) -
Klein Roger Davies,
Spaulding Caitlin,
Hultgren Scott
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.761.20
Subject(s) - pilus , bacterial adhesin , biology , microbiology and biotechnology , escherichia coli , virulence , virulence factor , fimbria , pilin , chaperone (clinical) , biofilm , bacteria , genetics , gene , medicine , pathology
Adhesion to biotic and abiotic surfaces is an essential step in the infectious cycle of many human pathogens. To this end, both Gram‐positive and Gram‐negative bacteria have developed a variety of strategies to overcome innate clearance mechanisms and persist within the host. The expression and biogenesis of Chaperone‐Usher Pathway (CUP) pili represent one such strategy. In addition to mediating the formation of bacterial biofilms, these proteinaceous extracellular appendages contain, at their tip, a two‐domain adhesin that is composed of an N‐terminal lectin domain and a C‐terminal pilin domain. The structure of the binding pocket within the lectin domain determines the specificity of that pilus for a given epitope. Individual Escherichia coli species encode and express up to 16 distinct CUP operons, each likely mediating a tropism for a specific habitat or environment within the host. While the importance of many of these pili, such as Type 1, P, and others, in human infection has been extensively elucidated, there still exist hundreds of pili across a broad range of bacterial species whose function has yet to be determined. Using a murine model of gastrointestinal infection, we have demonstrated that the F17‐Like (Ucl) pilus is an important virulence factor in the colonization of the gastrointestinal tract by E. coli species. Analysis of the distribution of this pilus type across E. coli clinical isolates reveals an enrichment in uropathogenic E. coli (UPEC) strains that cause recurrent urinary tract infection (rUTI). These findings suggest that the F17‐like pilus allows UPEC to persist in the gastrointestinal habitat before seeding the urinary tract. To probe the molecular mechanism of this attachment, we have obtained an X‐ray crystal structure of the adhesive domain of the F17‐Like pilus tip. Structural and biochemical comparison of this tip to other known bacterial adhesins involved in intestinal colonization indicates that the F17‐like pilus binds an epitope in the gastrointestinal tract that is distinct from both the Fim and F17 molecular receptor. Support or Funding Information This work was supported by Washington University MSTP Training Grant #5T32GM007200‐39, NIH/NIDDK R01 #AI048689, and the Department of Molecular Microbiology Sondra Schlesinger Graduate Student Fellowship