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Infect. Immun. doi:10.1128/IAI.00340-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

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

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

^* To whom correspondence should be addressed. Email: hultgren{at}borcim.wustl.edu.

	Abstract

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 (MSHA) 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 K. pneumoniae UTI pathogenesis compared to E. coli. 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.