Type 1 pilus-mediated bacterial invasion of bladder epithelial cells

Most strains of uropathogenic Escherichia coli (UPEC) encode filamentous ad hesive organelles called type 1 pili. We have determined that the type 1 pi lus adhesin, FimH, mediates not only bacterial adherence, but also invasion of human bladder epithelial cells. In contrast, adherence mediated by anot her pilus adhesin, PapG, did not initiate bacterial internalization. FimH-m ediated invasion required localized host actin reorganization, phosphoinosi tide 3-kinase (PI 3-kinase) activation and host protein tyrosine phosphoryl ation, but not activation of Src-family tyrosine kinases, Phosphorylation o f focal adhesin kinase (FAK) at Tyr397 and the formation of complexes betwe en FAK and PI 3-kinase and between a-actinin and vinculin were found to cor relate with type 1 pilus-mediated bacterial invasion. Inhibitors that preve nted bacterial invasion also blocked the formation of these complexes. Our results demonstrate that UPEC strains are not strictly extracellular pathog ens and that the type 1 pilus adhesin FimH can directly trigger host cell s ignaling cascades that lead to bacterial internalization.