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

Scott J. Weissman, Viktoriya Beskhlebnaya, Veronika Chesnokova, Sujay Chattopadhyay, Walter E. Stamm, Thomas M. Hooton, Evgeni V. Sokurenko

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3548-3555
Number of pages8
JournalInfection and immunity
Volume75
Issue number7
DOIs
StatePublished - Jul 2007

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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    Weissman, S. J., Beskhlebnaya, V., Chesnokova, V., Chattopadhyay, S., Stamm, W. E., Hooton, T. M., & Sokurenko, E. V. (2007). Differential stability and trade-off effects of pathoadaptive mutations in the Escherichia coli FimH adhesin. Infection and immunity, 75(7), 3548-3555. https://doi.org/10.1128/IAI.01963-06