| Autor: |
Hung, Chia-Suei, Bouckaert, Julie, Hung, Danielle, Pinkner, Jerome, Widberg, Charlotte, DeFusco, Anthony, Auguste, C. Gale, Strouse, Robert, Langermann, Solomon, Waksman, Gabriel, Hultgren, Scott J |
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| Zdroj: |
Molecular Microbiology; May2002, Vol. 44 Issue 4, p903-915, 13p |
| Abstrakt: |
Summary The first step in the colonization of the human urinary tract by pathogenic Escherichia coli is the mannose-sensitive binding of FimH, the adhesin present at the tip of type 1 pili, to the bladder epithelium. We elucidated crystallographically the interactions of FimH with D-mannose. The unique site binding pocket occupied by D-mannose was probed using site-directed mutagenesis. All but one of the mutants examined had greatly diminished mannose-binding activity and had also lost the ability to bind human bladder cells. The binding activity of the mono-saccharide D-mannose was delineated from this of mannotriose (Man(α 1–3)[Man(α 1–6)]Man) by gener-ating mutants that abolished D-mannose binding but retained mannotriose binding activity. Our structure/function analysis demonstrated that the binding of the monosaccharide α -D-mannose is the primary bladder cell receptor for uropathogenic E. coli and that this event requires a highly conserved FimH binding pocket. The residues in the FimH mannose-binding pocket were sequenced and found to be invariant in over 200 uropathogenic strains of E. coli . Only enterohaemorrhagic E. coli (EHEC) possess a sequence variation within the mannose-binding pocket of FimH, suggesting a naturally occurring mechanism of attenuation in EHEC bacteria that would prevent them from being targeted to the urinary tract. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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