Abstract
Urinary tract infections (UTIs), caused primarily by uropathogenic Escherichia coli (UPEC), are among the most common bacterial infections in humans, costing billions of dollars annually in medical expenses and causing significant morbidity with recurrent and chronic disease. Many details of the molecular pathogenesis of UPEC UTI have been unveiled through recent advances in a murine model of cystitis. Following ascension to the bladder, UPEC bind and invade superficial facet cells of the uroepithelium via type 1 pili. Uropathogens are able to evade innate cellular defences, in part, by proceeding through an intracellular cascade in which UPEC replicate within the facet cell cytoplasm, forming densely packed intracellular bacterial communities (IBCs). Egress of filamentous bacteria from IBCs can initiate subsequent rounds of IBC formation, thereby perpetuating acute infection. UPEC also invade the transitional epithelium, establishing latent, non-replicating reservoirs that resist antibiotic therapy and may initiate same-strain recurrent infection. UPEC employ a variety of additional molecular strategies to facilitate infection and to delay and subvert the host immune response. Finally, novel therapeutic and preventive strategies such as antivirulence compounds and vaccines may be necessary to combat the growing threat of antimicrobial resistance.
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