Differential stability and trade-off effects of pathoadaptive mutations in the Escherichia coli FimH adhesin

FimH is the tip adhesin of mannose-specific type 1 fimbriae of Escherichia coli, which are critical to the pathogenesis of urinary tract infections. Point FimH mutations increasing monomannose (1M)-specific uroepithelial adhesion are commonly found in uropathogenic strains of E. coli. Here, we demonstrate the emergence of a mixed population of clonally identical E. coli strains in the urine of a patient with acute cystitis, where half of the isolates carried a glycine-to-arginine substitution at position 66 of the mature FimH. The R66 mutation induced an unusually strong 1M-binding phenotype and a 20-fold advantage in mouse bladder colonization. However, E. coli strains carrying FimH-R66, but not the parental FimH-G66, had disappeared from the patient's rectal and urine samples collected from 29 to 44 days later, demonstrating within-host instability of the R66 mutation. No FimH variants with R66 were identified in a large (>600 strains) sequence database of fimH-positive E. coli strains. However, several strains carrying genes encoding FimH with either S66 or C66 mutations appeared to be relatively stable in the E. coli population. Relative to FimH-R66, the FimH-S66 and FimH-C66 variants mediated only moderate increases in 1M binding but preserved the ability to enhance binding under flow-induced shear conditions. In contrast, FimH-R66 completely lost shear-enhanced binding properties, with bacterial adhesion being inhibited by shear forces and lacking a rolling mode of binding. These functional trade-offs may determine the natural populational instability of this mutation or other pathoadaptive FimH mutations that confer dramatic increases in 1M binding strength. Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Weissman S.J.1 , Beskhlebnaya V. 2 , Chesnokova V. 3 , Chattopadhyay S.3 , Stamm W.E.4 , Hooton T.M.5 , Sokurenko E.V. 3, 6
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  • 1 Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, United States
  • 2 Department of Microbiology, Russian University of Peoples' Friendship, Moscow, Russian Federation
  • 3 Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, United States
  • 4 Division of Allergy and Infectious Disease, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, United States
  • 5 University of Miami Miller School of Medicine, Miami, FL 33136, United States
  • 6 Department of Microbiology, University of Washington School of Medicine, Box 357242, 1959 North Pacific Street, Seattle, WA 98195, United States
Ключевые слова
adhesin; arginine; glycine; mannose; protein fimH; unclassified drug; adaptation; animal cell; animal experiment; animal model; article; bacterial colonization; bacterial gene; bacterial strain; bacterium adherence; controlled study; cystitis; Escherichia coli; female; fimbria; gene mutation; mouse; nonhuman; phenotype; priority journal; urinary tract infection; Adaptation, Physiological; Adhesins, Escherichia coli; Amino Acid Sequence; Animals; Animals, Newborn; Bacterial Adhesion; Base Sequence; Cystitis; Escherichia coli; Escherichia coli Infections; Fimbriae Proteins; Humans; Mannose; Mice; Mice, Inbred C3H; Molecular Sequence Data; Mutation; Stress, Mechanical; Urinary Tract Infections
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Bronnikov K.A., Fabris J.C., Gonçalves S.V.B.
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