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Infection and Immunity, July 2007, p. 3548-3555, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.01963-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Differential Stability and Trade-Off Effects of Pathoadaptive Mutations in the Escherichia coli FimH Adhesin ^,

Scott J. Weissman,^1, Viktoriya Beskhlebnaya,^2, Veronika Chesnokova,³ Sujay Chattopadhyay,³ Walter E. Stamm,⁴ Thomas M. Hooton,⁵ and Evgeni V. Sokurenko^3*

Division of Infectious Disease, Children's Hospital and Regional Medical Center; Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington 98195,¹ Department of Microbiology, Russian University of Peoples’ Friendship, Moscow, Russia,² Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195,³ Division of Allergy and Infectious Disease, Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195,⁴ University of Miami Miller School of Medicine, Miami, Florida 33136⁵

Received 14 December 2006/ Returned for modification 23 February 2007/ Accepted 2 May 2007

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.

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* Corresponding author. Mailing address: Department of Microbiology, University of Washington School of Medicine, 1959 North Pacific Street, Box 357242, Seattle, WA 98195. Phone: (206) 685-2162. Fax: (206) 543-8297. E-mail: evs{at}u.washington.edu

Published ahead of print on 14 May 2007.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: V. J. DiRita

S.J.W. and V.B. contributed equally to this work.

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Infection and Immunity, July 2007, p. 3548-3555, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.01963-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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