Strengths and Limitations of Model Systems for the Study of Urinary Tract Infections and Related Pathologies

Abstract

SUMMARYUrinary tract infections (UTIs) are some of the most common bacterial infections worldwide and are a source of substantial morbidity among otherwise healthy women. UTIs can be caused by a variety of microbes, but the predominant etiologic agent of these infections is uropathogenicEscherichia coli(UPEC). An especially troubling feature of UPEC-associated UTIs is their high rate of recurrence. This problem is compounded by the drastic increase in the global incidence of antibiotic-resistant UPEC strains over the past 15 years. The need for more-effective treatments for UTIs is driving research aimed at bettering our understanding of the virulence mechanisms and host-pathogen interactions that occur during the course of these infections. Surrogate models of human infection, including cell culture systems and the use of murine, porcine, avian, teleost (zebrafish), and nematode hosts, are being employed to define host and bacterial factors that modulate the pathogenesis of UTIs. These model systems are revealing how UPEC strains can avoid or overcome host defenses and acquire scarce nutrients while also providing insight into the virulence mechanisms used by UPEC within compromised individuals, such as catheterized patients. Here, we summarize our current understanding of UTI pathogenesis while also giving an overview of the model systems used to study the initiation, persistence, and recurrence of UTIs and life-threatening sequelae like urosepsis. Although we focus on UPEC, the experimental systems described here can also provide valuable insight into the disease processes associated with other bacterial pathogens both within the urinary tract and elsewhere within the host.

Bacterial virulence phenotypes of Escherichia coli and host susceptibility determine risk for urinary tract infections

“…Mouse models of UTI recapitulate the histological markers of human UTIs and multiple mouse models have been developed that each reflect a portion of the diversity of UTI pathology seen in the clinic [reviewed in (59, 60)]. Consistent with their ability to cause UTIs in humans, many of our UAEC strains were able to elicit key hallmarks of human pathogenesis in mouse models of UTI, including acute cystitis, the formation of IBCs, the development of chronic cystitis, and persistence in quiescent intracellular reservoirs.…”

Urinary Tract Infection: Pathogenesis and Outlook

“…Other etiologies include infections from Staphylococcus, Klebsiella, Enterobacter, Proteus , and Enterococcus ; these organisms become particularly relevant during catheter-associated and hospital-acquired infections [7]. The pathogenic cascade of UPEC cystitis has been extensively studied in recent years, largely in cell-culture and mouse models, as mice recapitulate many facets of the bladder epithelial environment (reviewed in [8]). Through these studies, unprecedented light has been shed on the molecular and cellular basis of infection.…”

P2X1, P2X4, and P2X7 Receptor Knock Out Mice Expose Differential Outcome of Sepsis Induced by α-Haemolysin Producing Escherichia coli

“…However, direct injection of uropathogenic bacteria intravenously has been proven to be a beneficial model for urosepsis (Barber et al, 2016). The chosen uropathogenic bacterium (ARD6, O6:K13:H1) commonly causes urinary tract infection in humans and, in addition to HlyA, also expresses other virulence enhancing proteins such as P-fimbriae (Zingler et al, 1992).…”