Uropathogenic Escherichia coli potentiates type 1 pilus-induced apoptosis by suppressing NF-kappa B

Urinary tract infections (UTIs) are among the most common inflammatory dise ases. Acute UTIs are typically caused by type 1-piliated Escherichia coli a nd result in urothelial apoptosis, local cytokine release, and neutrophil i nfiltration. To examine the urothelial apoptotic response, a human urotheli al cell line was incubated with various E. coli isolates and was then chara cterized by flow cytometry. Uropathogenic E. coli (UPEC) induced rapid urot helial apoptosis that was strictly dependent upon interactions mediated by type 1 pili. Interestingly, nonpathogenic HB101 E. coli expressing type I p ili induced apoptosis at approximately 50% of the level induced by UPEC, su ggesting that pathogenic strains contribute to apoptosis by pilus-independe nt mechanisms. Consistent with this possibility, UPEC blocked activity of a n NF-kappaB-dependent reporter in response to inflammatory stimuli, yet thi s effect was independent of functional type I pili and was not mediated by laboratory strains of E. coli. UPEC suppressed NF-kappaB by stabilizing I k appaB alpha., and UPEC rapidly altered cellular signaling pathways. Finally , blocking NF-kappaB activity increased the level of piliated HB101-induced apoptosis to the level of apoptosis induced by UPEC. These results suggest that UPEC blocks NF-kappaB and thereby enhances type 1 pili-induced apopto sis as a component of the uropathogenic program.