Essential role for the urothelial plaque in Gram-negative urinary tract infections.

Over 90% of urinary tract infections (UTI) are caused by Gram-negative bacteria, especially uropathogenic Escherichia coli (UPEC). Bladder superficial cells produce Uroplakin (Upk) containing urothelial plaques that bind to UPEC type I fimbriae. The role of the plaque in UPEC urothelial invasion and triggering the host inflammatory response remains unclear. In this study, we used Upk1b KO mice to test the hypothesis that a functional urothelial plaque is required for UPEC UTI. Following UPEC inoculation, Upk1b KO mice exhibited reduced bacterial burden, impaired urothelial invasion, and absent intracellular bacterial communities, compared to wild-type hosts. Transcriptome analysis identified attenuation of innate immune pathways in Upk1b KO bladders and flow cytometry confirmed limited phagocyte recruitment. Our results demonstrate that the plaque is essential for UPEC urothelial invasion, establishment of UTI, and initiation of the innate immune response. Notable study limitations include the potential that observations made in mouse models are associative rather than causal and that our conclusions may not fully apply to human UTI. While our findings strengthen the rationale for targeted therapies that disrupt UPEC-plaque interactions, such strategies may prove challenging given the fundamental role of the plaque in preserving urothelial integrity and barrier function.