Tamm-Horsfall protein binds to type 1 fimbriated Escherichia coli and prevents E. coli from binding to uroplakin Ia and Ib receptors
Tamm-Horsfall protein binds to type 1 fimbriated Escherichia coli and prevents E. coli from binding to uroplakin Ia and Ib receptors
复制标题
DOI：
10.1074/jbc.m008610200
复制
发表时间：
2001-03-30
影响因子：
4.8
通讯作者：
Wu, XR
中科院分区：
文献类型：
--
作者：
Pak, J;Pu, YB;Wu, XR
致病性大肠杆菌粘附于尿路上皮表面是尿路感染（UTI）发病机制的关键第一步，其粘附受三个关键因素控制：大肠杆菌粘附素、宿主受体和宿主防御机制。尽管人们对E.大肠杆菌粘附素及其尿路上皮受体的研究，对宿主防御在粘附过程中的作用知之甚少，本文证明Tamm-Horsfall蛋白（THP）是与1型菌毛大肠杆菌特异性结合的主要尿蛋白。该结合具有高度的特异性和饱和性，可被D-甘露糖抑制，并可被THP的内切糖苷酶H处理所消除，表明该结合是由THP的高甘露糖部分介导的。此外，与健康个体大肠分离物中流行的1型菌毛FimH粘附素相比，携带1型菌毛FimH粘附素的表型变体的大肠杆菌菌株与THP的结合要大得多。最后，生理浓度的THP完全消除了1型菌毛化大肠杆菌的结合。这些结果在功能水平上证实THP含有能够与1型菌毛特异性相互作用的保守的高甘露糖部分，并强烈表明这种主要的尿糖蛋白是一种关键的尿抗粘附因子，用于防止1型菌毛大肠杆菌与尿路上皮受体结合。
The adherence of uropathogenic Escherichia coli to the urothelial surface, a critical first step in the pathogenesis of urinary tract infection (UTI), is controlled by three key elements: E, coli adhesins, host receptors, and host defense mechanisms. Although much has been learned about E. coli adhesins and their urothelial receptors, little is known about the role of host defense in the adherence process, Here we show that Tamm-Horsfall protein (THP) is the principal urinary protein that binds specifically to type 1 fimbriated E. coli, the main cause of UTI, The binding was highly specific and saturable and could be inhibited by D-mannose and abolished by endoglycosidase H treatment of THP, suggesting that the binding is mediated by the high-mannose moieties of THP, It is species-conserved, occurring in both human and mouse THPs. In addition, the binding to THP was much greater with an E, coli strain bearing a phenotypic variant of the type 1 fimbrial FimH adhesin characteristic of those prevalent in UTI isolates compared with the one prevalent in isolates from the large intestine of healthy individuals, Finally, a physiological concentration of THP completely abolished the binding of type 1 fimbriated E. coli to uroplakins Ia and Ib, two putative urothelial receptors for type 1 fimbriae, These results establish, on a functional level, that THP contains conserved high-mannose moieties capable of specific interaction with type 1 fimbriae and strongly suggest that this major urinary glycoprotein is a key urinary anti-adherence factor serving to prevent type 1 fimbriated E, coli from binding to the urothelial receptors.