Establishment of a Persistent <i>Escherichia coli</i> Reservoir during the Acute Phase of a Bladder Infection

TLDR

Urinary tract infections are mainly caused by uropathogenic E. coli that express type 1 pili, which mediate attachment to and invasion of bladder epithelial cells, while infected superficial cells are shed by exfoliation. The study seeks to elucidate how type 1 pilus‑mediated invasion drives urinary tract infection pathogenesis. The authors demonstrate that type 1‑piliated uropathogens invade superficial bladder cells, replicate into bacterial factories, and then reemerge to establish a persistent, quiescent reservoir in the mucosa that can seed recurrent infections.

Abstract

ABSTRACT The vast majority of urinary tract infections are caused by strains of uropathogenic Escherichia coli that encode filamentous adhesive organelles called type 1 pili. These structures mediate both bacterial attachment to and invasion of bladder epithelial cells. However, the mechanism by which type 1 pilus-mediated bacterial invasion contributes to the pathogenesis of a urinary tract infection is unknown. Here we show that type 1-piliated uropathogens can invade the superficial epithelial cells that line the lumenal surface of the bladder and subsequently replicate, forming massive foci of intracellular E. coli termed bacterial factories. In response to infection, superficial bladder cells exfoliate and are removed with the flow of urine. To avoid clearance by exfoliation, intracellular uropathogens can reemerge and eventually establish a persistent, quiescent bacterial reservoir within the 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.