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Infection and Immunity, July 2008, p. 3346-3356, Vol. 76, No. 7
0019-9567/08/$08.00+0     doi:10.1128/IAI.00340-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Molecular Variations in Klebsiella pneumoniae and Escherichia coli FimH Affect Function and Pathogenesis in the Urinary Tract{triangledown}

David A. Rosen, Jerome S. Pinkner, Jennifer N. Walker, Jennifer Stine Elam, Jennifer M. Jones, and Scott J. Hultgren*

Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110

Received 14 March 2008/ Returned for modification 17 April 2008/ Accepted 29 April 2008

Type 1 pili mediate binding, invasion, and biofilm formation of uropathogenic Escherichia coli (UPEC) in the host urothelium during urinary tract infection (UTI) via the adhesin FimH. In this study, we characterized the molecular basis of functional differences between FimH of the UPEC isolate UTI89 and the Klebsiella pneumoniae cystitis isolate TOP52. Type 1 pili characteristically mediate mannose-sensitive hemagglutination of guinea pig erythrocytes. Although the adhesin domain of K. pneumoniae TOP52 FimH (FimH52) is highly homologous to that of E. coli, with an identical mannose binding pocket and surrounding hydrophobic ridge, it lacks the ability to agglutinate guinea pig erythrocytes. In addition, FimH-dependent biofilm formation in K. pneumoniae is inhibited by heptyl mannose, but not methyl mannose, suggesting the need for contacts outside of the mannose binding pocket. The binding specificity differences observed for FimH52 resulted in significant functional differences seen in the pathogenesis of K. pneumoniae UTI compared to E. coli UTI. Infections in a murine model of UTI demonstrated that although the K. pneumoniae strain TOP52 required FimH52 for invasion and IBC formation in the bladder, FimH52 was not essential for early colonization. This work reveals that a limited amount of sequence variation between the FimH of E. coli and K. pneumoniae results in significant differences in function and ability to colonize the urinary tract.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Microbial Pathogenesis, Box 8230, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110. Phone: (314) 362-6772. Fax: (314) 362-1998. E-mail: hultgren{at}borcim.wustl.edu

{triangledown} Published ahead of print on 12 May 2008.

Editor: A. J. Bäumler

Infection and Immunity, July 2008, p. 3346-3356, Vol. 76, No. 7
0019-9567/08/$08.00+0     doi:10.1128/IAI.00340-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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