Localization of a Domain in the FimH Adhesin of Escherichia Coli Type 1 Fimbriae Capable of Receptor Recognition and Use of a Domain-Specific Antibody to Confer Protection Against Experimental Urinary Tract Infection
| Autor: | Bereneice Madison, Ankur H. Shah, Ravi Malaviya, Prabhu M. Arumugam, Teruo Ikeda, Soman N. Abraham, Krishnan Thankavel |
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| Rok vydání: | 1998 |
| Předmět: |
Monosaccharide Transport Proteins
Urinary system Urology Urinary Bladder Fimbria Biology Cross Reactions medicine.disease_cause Epitope Bacterial Adhesion Maltose-Binding Proteins Fimbriae Proteins Microbiology Mice Escherichia coli medicine Animals Adhesins Bacterial Receptor Cells Cultured Adhesins Escherichia coli Mice Inbred ICR business.industry Escherichia coli Proteins Immunization Passive A domain General Medicine Fusion protein Antibodies Bacterial Virology Bacterial adhesin Specific antibody Fimbriae Bacterial Periplasmic Binding Proteins Urinary Tract Infections biology.protein ATP-Binding Cassette Transporters Female Antibody Carrier Proteins business Binding domain Research Article |
| Zdroj: | The Journal of Urology. :1417-1418 |
| ISSN: | 0022-5347 |
| DOI: | 10.1097/00005392-199804000-00140 |
| Popis: | The FimH subunit of type 1-fimbriated Escherichia coli has been implicated as an important determinant of bacterial adherence and colonization of the urinary tract. Here, we sought to localize the functionally important domain(s) within the FimH molecule and to determine if antibodies against this domain would block adherence of type 1-fimbriated E. coli to the bladder mucosa in situ and in vivo in an established mouse model of cystitis. We generated translational fusion proteins of disparate regions of the FimH molecule with an affinity tag MalE, and tested each of the fusion products in vitro for functional activity. The minimum region responsible for binding mouse bladder epithelial cells and a soluble mannoprotein, horseradish peroxidase, was contained within residues 1-100 of the FimH molecule. We validated and extended these findings by demonstrating that antibodies directed at the putative binding region of FimH or at synthetic peptides corresponding to epitopes within the binding domain could specifically block type 1 fimbriae-mediated bacterial adherence to bladder epithelial cells in situ and yeast cells in vitro. Next, we compared the ability of mice passively immunized intraperitoneally with antisera raised against residues 1-25 and 253-264 of FimH or 1-13 of FimA to resist bladder colonization in vivo after intravesicular challenge with type 1-fimbriated E. coli. Only the antibody directed at the putative binding region of FimH (anti- s-FimH1-25) significantly reduced E. coli bladder infections in the experimental mouse model of urinary tract infections. Similar results were obtained when the mice were actively immunized with synthetic peptides corresponding to residues 1-25 and 253-264 of FimH or 1-13 of FimA. The mechanism of protection was attributed, at least in part, to inhibition of bacterial adherence to the bladder surface by s-FimH1-25-specific antibody molecules that had filtered through the kidneys into the urine. The level of FimH antibodies entering the bladder from the circulatory system of the immunized mice was found to be markedly enhanced upon bacterial challenge. The potential broad spectrum activity of the protective FimH antibody was indicated from its serologic cross-reactivity with various urinary tract bacterial isolates bearing type 1 fimbriae. These findings could be relevant in the design of an efficacious and broadly reactive FimH vaccine against urinary tract infections. |
| Databáze: | OpenAIRE |
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