Establishment of a persistent Escherichia coli reservoir during the acute phase of a bladder infection

The vast majority of urinary tract infections are caused by strains of urop athogenic Escherichia coli that encode filamentous adhesive organelles call ed type I pill. These structures mediate both bacterial attachment to and i nvasion of bladder epithelial cells. However, the mechanism by which type 1 pilus-mediated bacterial invasion contributes to the pathogenesis of a uri nary tract infection is unknown. Here we show that type 1-piliated uropatho gens can invade the superficial epithelial cells that line the lumenal surf ace of the bladder and subsequently replicate, forming massive foci of intr acellular E, coli termed bacterial factories. In response to infection, sup erficial bladder cells exfoliate and are removed with the how of urine. To avoid clearance by exfoliation, intracellular uropathogens can reemerge and eventually establish a persistent, quiescent bacterial reservoir within th e bladder mucosa that may serve as a source for recurrent acute infections. These observations suggest that urinary tract infections are more chronic and invasive than generally assumed.