Interaction of Dr adhesin with collagen type IV is a critical step in Escherichia coli renal persistence.
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 < or = 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.
Selvarangan
Rangaraj
R
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, 77555-1062, USA.
Goluszko
Pawel
P
Singhal
Jyotsana
J
Carnoy
Christophe
C
Moseley
Steve
S
Hudson
Billy
B
Nowicki
Stella
S
Nowicki
Bogdan
B
D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018958:CD55 Antigens / Q000378:metabolism; D002908:Chronic Disease; D024141:Collagen Type IV / Q000378:metabolism*; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology / Q000503:physiopathology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007668:Kidney / Q000382:microbiology; D051379:Mice; D008809:Mice, Inbred C3H; D011704:Pyelonephritis / Q000382:microbiology / Q000503:physiopathology*; D014774:Virulence
D018829:Adhesins, Bacterial; D018958:CD55 Antigens; D024141:Collagen Type IV; C465563:DraE protein, E coli; D029968:Escherichia coli Proteins