Development of experimental model of chronic pyelonephritis with Escherichia coli O75:K5:H-bearing Dr fimbriae - Mutation in the dra region prevented tubulointerstitial nephritis
Development of experimental model of chronic pyelonephritis with Escherichia coli O75:K5:H-bearing Dr fimbriae - Mutation in the dra region prevented tubulointerstitial nephritis
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DOI：
10.1172/jci119329
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发表时间：
1997-04-01
影响因子：
15.9
通讯作者：
Nowicki, B
中科院分区：
文献类型：
--
作者：
Goluszko, P;Moseley, SL;Nowicki, B
表达Dr菌毛和相关粘附素的大肠杆菌识别共同受体衰变加速因子。E.据推测，表达Dr家族粘附素的大肠杆菌菌株与膀胱炎（30-50%）、妊娠相关肾盂肾炎（30%）和慢性腹泻（50%）有关。在这项研究中，我们调查的假设，E。大肠杆菌DR粘附素介导的肾间质结合可能在慢性肾盂肾炎的发生中起重要作用。coliDR 14，临床大肠埃希菌DR 14。构建了携带Dr菌毛的大肠杆菌分离株IH 11128，并用于描述上行性肾盂肾炎实验模型中感染的持续性和间质嗜性。肾匀浆定量培养结果表明，Dr血凝素阳性（Dr+）E. coli IH 11128在肾组织中建立了1年的定殖。在Dr血凝素阴性（Dr-）组中，50%的动物在20周内清除感染，100%在32至52周之间。Dr+ E.大肠杆菌定植于肾间质。在Dr+组的肾组织中发现了与肾小管间质性肾炎对应的显著组织学变化，包括间质性炎症、纤维化和肾小管萎缩，但在Dr-组中未发现。在受间质性炎症和纤维化影响的实质区域检测到大量的菌毛抗原。这一结果与假设一致，即突变的dra区域内，影响E。大肠杆菌与肾小管基底膜结合，阻止了肾间质嗜性和肾小管间质性肾炎特征性变化的发生。
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.