Uroplakin Ia is the urothelial receptor for uropathogenicEscherichia coli: evidence from in vitro FimH binding

作者：Ge Zhou, Wenjun Mo, Peter Sebbel, Guangwei Min, Thomas A. Neubert, Rudi Glockshuber, Xue‐Ru Wu, Tung‐Tien Sun, Xiang‐Peng Kong · 发表于：Journal of Cell Science · 年份：2001 · DOI：10.1242/jcs.114.22.4095 · 被引用次数：377 · 研究领域：Bladder and Urothelial Cancer Treatments、Urinary Tract Infections Management、Infectious Disease Case Reports and Treatments

The binding of uropathogenic Escherichia coli to the urothelial surface is a crucial initial event for establishing urinary tract infection because it allows the bacteria to gain a foothold on the urothelial surface, thus preventing them from being removed by micturition. In addition, it triggers bacterial invasion as well as host urothelial defense. This binding is mediated by the FimH adhesin located at the tip of the bacterial type 1-fimbrium, a filamentous attachment apparatus, and its urothelial receptor. We have prepared a biotinylated, recombinant FimH-FimC adhesin:chaperone complex and used it to identify its mouse urothelial receptor. The FimH-FimC complex binds specifically to a single 24 kDa major mouse urothelial plaque protein, which we identified as uroplakin Ia by mass spectrometry, cDNA cloning and immunoreactivity. The terminal mannosyl moieties on Asn-169 of uroplakin Ia are responsible for FimH as well as concanavalin A binding. Although FimH binds to uroplakin Ia with only moderate strength (K(d) approximately 100 nM between pH 4 and 9), the binding between multiple fimbriae of a bacterium and the crystalline array of polymerized uroplakin receptors should achieve high avidity and stable bacterial attachment. The FimH-FimC complex binds preferentially to the mouse urothelial umbrella cells in a pattern similar to uroplakin staining. Our results indicate that the structurally related uroplakins Ia and Ib are glycosylated differently, that uroplakin Ia serve...