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Infection and Immunity, August 2004, p. 4827-4835, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4827-4835.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Interaction of Dr Adhesin with Collagen Type IV Is a Critical Step in Escherichia coli Renal Persistence

Rangaraj Selvarangan,1 Pawel Goluszko,1 Jyotsana Singhal,1 Christophe Carnoy,2 Steve Moseley,3 Billy Hudson,4 Stella Nowicki,1 and Bogdan Nowicki1*

Departments of Obstetrics and Gynecology and Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555-1062,1 Institute de Biologie de Lille, Lille, France,2 University of Washington, Seattle, Washington,3 Departments of Medicine and Biochemistry, Vanderbilt University, Nashville, Tennessee4

Received 22 October 2003/ Returned for modification 6 February 2004/ Accepted 21 April 2004

The pathogenic mechanism of recurrent or chronic urinary tract infection is poorly understood. Escherichia coli cells bearing Dr fimbriae display unique tropism to the basement membrane (BM)-renal interstitium that enables the bacteria to cause chronic pyelonephritis in experimental mice. The renal receptors for Dr-fimbriated E. coli are type IV collagen and decay-accelerating factor (DAF). We hypothesized that type IV collagen receptor-mediated BM-interstitial tropism is essential for E. coli to cause chronic pyelonephritis. To test the role of the type IV collagen tropism of Dr-fimbriated E. coli in renal persistence, we constructed an isogenic mutant in the DraE adhesin subunit that was unable to bind type IV collagen but retained binding to DAF and examined its virulence in the mouse model. The collagen-binding mutant DrI113T was eliminated from the mouse renal tissues in 6 to 8 weeks, while the parent strain caused persistent renal infection that lasted at least 14 weeks (P ≤ 0.02). Transcomplementation with the intact Dr operon restored collagen-binding activity, BM-interstitial tropism, and the ability to cause persistent renal infection. We conclude that type IV collagen binding mediated by DraE adhesin is a critical step for the development of persistent renal infection in a murine model of E. coli pyelonephritis.

* Corresponding author. Mailing address: Department of Obstetrics and Gynecology, Medical Research Building, University of Texas Medical Branch, Galveston, TX 77555-1062. Phone: (409) 772-7599. Fax: (409) 747-0475. E-mail: bnowicki{at}utmb.edu.

Editor: V. J. DiRita

Infection and Immunity, August 2004, p. 4827-4835, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4827-4835.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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