Colonization of renal interstitial tissue with escherichia coll 075:K5:h-bearing dr fimbriae: mutation in the dra operon prevented tubulointerstitial nephritis

ObjeçtivcLf"- colt that express Dr colonization factors has been recently found in 30% of patients with gestational pyelonephritis. In this study, we investigated the hypothesis that renal interstitial binding mediated by the E. cou Dr adhesin in vitro, may be important for the development of interstitial colonization resulting in tubulointerstitial nephritis in vivo. Studyjbesign: An insertional dra mutant of clinical E. coli IH11128 bearing Dr fimbriae was constructed using a suicide vector pGP704. The resulting mutant E. coli IH1128 Dr" lost its attachment capacity to interstitium. The Dr+ parent strain and Dr~ E. coli mutant were used to characterize persistence of infection and associated histological lesions in an experimental model of ascending pyelonephritis. Results: The Dr+ E. call established a long term (52 weeks) colonization of renal tissue. In the Dr~ group, 50% of animals cleared infection within 20 weeks and 100% between 32 to 51 weeks. In the Dr+ group, E. coli cells were found to colonize the renal interstitium (detected by hematoxylin-eosin and immuno staining). Fimbrial antigen was detected in the parenchymal regions affected by tubulointerstitial nephritis but not in the non-affected tissue. Histological changes in the Dr+ group included interstitial inflammation, interstitial fibrosis, and tubular atrophy in the kidney tissue. In the Dr~ group, histological lesions were significantly less severe than those of the Dr+ group and involved a smaller number of animals. Conclusions: The obtained results are consistent with the hypothesis that mutation within the dra region, coding for Dr fimbriae, a factor that mediates binding to renal interstitium, prevents the development of the renal changes characteristically seen in tubulointerstitial nephritis. It remains to be investigated whether the gestational pyelonephritis may contribute to long term complications including hypertension and end stage renal disease. Supported by NIH Grant ROIDK42029 (BN).