Uroepithelial defense has ben suggested to contribute to the local host resistance against ascending urinary tract infection. The cellular mechanism, however, is not known. In this study, bacterial growth was measured under the direct and indirect influence of uroepithelial cells. To study if a specific ligand-receptor interaction is required for uroepithelial cell (UEC) activation, isogenic Escherichia coli mutants expressing either mannose-sensitive, mannose-resistant (p), or mannose resistant (s) pili were tested for their capacity to induce the UEC defense mechanism. The antibacterial effect of UEC was abolished either by performing coculture in chambers with a fluid-permeable membrane which separates UEC from bacteria or by inhibiting membrane contact using the antiadherence factor pentosane polysulfate. No difference between the various types of pili could be shown. All E. coli strains adhered comparably to the UEC and were subsequently suppressed in their growth. Even a "naked" mutant without expression of common pili showed a similar behavior. In conclusion, bacterial growth suppression depends on direct contact between the UEC and bacteria, but is independent of common pili expressed on E. coli.