Development of experimental model of chronic pyelonephritis with Escherichia coli O75:K5:H-bearing Dr fimbriae: mutation in the dra region prevented tubulointerstitial nephritis.

Escherichia coli that express Dr fimbriae and related adhesins recognize the common receptor decay accelerating factor. E. coli strains that express adhesins of the Dr family were postulated to be associated with cystitis (30-50%), pregnancy-associated pyelonephritis (30%), and chronic diarrhea (50%). In this study, we investigated the hypothesis that E. coli renal interstitial binding mediated by the Dr adhesin may be important for the development of chronic pyelonephritis. An insertional dra mutant, E. coli DR14, of the clinical E. coli isolate IH11128 bearing Dr fimbriae, was constructed and used to characterize persistence of infection and interstitial tropism in an experimental model of ascending pyelonephritis. Quantitative cultures of kidney homogenates indicated that Dr hemagglutinin positive (Dr+) E. coli IH11128 established a 1-yr colonization of renal tissue. In the Dr hemagglutinin negative (Dr-) group, 50% of animals cleared infection within 20 wk and 100% between 32 to 52 wk. Dr+ E. coli colonized the renal interstitium. Significant histological changes corresponding to tubulointerstitial nephritis including interstitial inflammation, fibrosis, and tubular atrophy were found in the kidney tissue of the Dr+ but not the Dr- group. A substantial amount of fimbrial antigen was detected in the parenchymal regions affected by interstitial inflammation and fibrosis. The obtained results are consistent with the hypothesis that mutation within the dra region, affecting E. coli binding to tubular basement membranes, prevented renal interstitial tropism and the development of the changes characteristically seen in tubulointerstitial nephritis.