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Journal of Bacteriology, November 2009, p. 6592-6601, Vol. 191, No. 21
0021-9193/09/$08.00+0     doi:10.1128/JB.00786-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Comparative Structure-Function Analysis of Mannose-Specific FimH Adhesins from Klebsiella pneumoniae and Escherichia coli{triangledown}

Steen G. Stahlhut,1,{dagger} Veronika Tchesnokova,2,{dagger} Carsten Struve,1 Scott J. Weissman,2 Sujay Chattopadhyay,2 Olga Yakovenko,3 Pavel Aprikian,2 Evgeni V. Sokurenko,2* and Karen Angeliki Krogfelt1*

Department of Bacteriology, Mycology and Parasitology, Statens Serum Institut, 2300 Copenhagen S, Denmark,1 Departments of Microbiology,2 Bioengineering, University of Washington School of Medicine, Seattle, Washington 981953

Received 16 June 2009/ Accepted 27 August 2009

FimH, the adhesive subunit of type 1 fimbriae expressed by many enterobacteria, mediates mannose-sensitive binding to target host cells. At the same time, fine receptor-structural specificities of FimH from different species can be substantially different, affecting bacterial tissue tropism and, as a result, the role of the particular fimbriae in pathogenesis. In this study, we compared functional properties of the FimH proteins from Escherichia coli and Klebsiella pneumoniae, which are both 279 amino acids in length but differ by some ~15% of residues. We show that K. pneumoniae FimH is unable to mediate adhesion in a monomannose-specific manner via terminally exposed Man{alpha}(1-2) residues in N-linked oligosaccharides, which are the structural basis of the tropism of E. coli FimH for uroepithelial cells. However, K. pneumoniae FimH can bind to the terminally exposed Man{alpha}(1-3)Manβ(1-4)GlcNAcβ1 trisaccharide, though only in a shear-dependent manner, wherein the binding is marginal at low shear force but enhanced sevenfold under increased shear. A single mutation in the K. pneumoniae FimH, S62A, converts the mode of binding from shear dependent to shear independent. This mutation has occurred naturally in the course of endemic circulation of a nosocomial uropathogenic clone and is identical to a pathogenicity-adaptive mutation found in highly virulent uropathogenic strains of E. coli, in which it also eliminates the dependence of E. coli binding on shear. The shear-dependent binding properties of the K. pneumoniae and E. coli FimH proteins are mediated via an allosteric catch bond mechanism. Thus, despite differences in FimH structure and fine receptor specificity, the shear-dependent nature of FimH-mediated adhesion is highly conserved between bacterial species, supporting its remarkable physiological significance.

* Corresponding author. Mailing address for Evgeni V. Sokurenko: Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195. Phone: (206) 685-2162. Fax: (206) 543-8297. E-mail: evs{at}u.washington.edu. Mailing address for Karen Angeliki Krogfelt: Department of Bacteriology, Mycology and Parasitology, Statens Serum Institut, 2300 Copenhagen S, Denmark. Phone: 45 32683745. Fax: 45 32688238. E-mail: kak{at}ssi.dk

{triangledown} Published ahead of print on 4 September 2009.

{dagger} Contributed equally to this work.

Journal of Bacteriology, November 2009, p. 6592-6601, Vol. 191, No. 21
0021-9193/09/$08.00+0     doi:10.1128/JB.00786-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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