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

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 pre venting them from being removed by micturition. In addition, it triggers ba cterial invasion as well as host urothelial defense. This binding is mediat ed by the FimH adhesin located at the tip of the bacterial type 1-fimbrium, a filamentous attachment apparatus, and its urothelial receptor. We have p repared a biotinylated, recombinant FimH-FimC adhesin: chaperone complex an d 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 an d immunoreactivity. The terminal mannosyl moieties on Asn-169 of uroplakin Ia are responsible for FimH as well as concanavalin A binding. Although Fim H binds to uroplakin Ia with only moderate strength (K-d similar to 100 nM between pH 4 and 9), the binding between multiple fimbriae of a bacterium a nd the crystalline array of polymerized uroplakin receptors should achieve high avidity and stable bacterial attachment. The FimH-FimC complex binds p referentially to the mouse urothelial umbrella cells in a pattern similar t o uroplakin staining. Our results indicate that the structurally related ur oplakins Ia and Ib are glycosylated differently, that uroplakin Ia serves a s the urothelial receptor for the type 1-fimbriated E. coli, and that the b inding of uropathogenic bacteria to uroplakin Ia may play a key role in med iating the urothelial responses to bacterial attachment.