Urinary tract infection of mice to model human disease: Practicalities, implications and limitations

Carey, Alison J.; Tan, Chee K.; Ipe, Deepak S.; Sullivan, Matthew J.; Cripps, Allan W.; Schembri, Mark A.; Ulett, Glen C.

doi:10.3109/1040841x.2015.1028885

Cited by 44 publications

(48 citation statements)

References 264 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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Urinary tract infections (UTIs) are caused by uropathogenic Escherichia coli (UPEC) strains. In contrast to many enteric E. coli pathogroups, no genetic signature has been identified for UPEC strains. We conducted a high-resolution comparative genomic study using E. coli isolates collected from the urine of women suffering from frequent recurrent UTIs. These isolates were genetically diverse and varied in urovirulence, or the ability to infect the bladder of a mouse model of cystitis. Importantly, we found no set of genes, including previously defined putative urovirulence factors (PUFs), that were predictive of urovirulence. In addition, in some patients, the E. coli strain causing a recurrent UTI had fewer PUFs than the supplanted strain. In competitive experimental infections in mice, the supplanting strain was more efficient at colonizing the mouse bladder than the supplanted strain. Despite the lack of a clear genomic signature for urovirulence, comparative transcriptomic and phenotypic analyses revealed that the expression of key conserved functions during culture, such as motility and sugar metabolism, could be used to predict subsequent mouse bladder colonization. Taken together, our findings suggest that UTI risk and outcome may be determined by complex interactions between host susceptibility and the urovirulence potential of diverse bacterial strains.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…Two of the most important independent risk factors for UTI in sexually active premenopausal women are a history of rUTI (two or more episodes) 4 and a first UTI at age ≤15 years 5 . However, experimental models of UTI have largely been limited to animals without prior infections 6–8 , so how infection history impacts the risk for and outcome of rUTI remains poorly understood. To elucidate the molecular interplay between infection history and increased susceptibility to rUTI, we investigated molecular mechanisms in a mouse model of recurrent cystitis (bladder infection) (Fig.…”

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confidence: 99%

A mucosal imprint left by prior Escherichia coli bladder infection sensitizes to recurrent disease

et al. 2016

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Recurrent bacterial infections are a significant burden worldwide, and prior history of infection is often a significant risk factor for developing new infections. For urinary tract infection (UTI), a history of two or more episodes is an independent risk factor for acute infection. However, mechanistic knowledge of UTI pathogenesis has come almost exclusively from studies in naive mice. Here we show that, in mice, an initial Escherichia coli UTI, whether chronic or self-limiting, leaves a long-lasting molecular imprint on the bladder tissue that alters the pathophysiology of subsequent infections, affecting host susceptibility and disease outcome. In bladders of previously infected versus non-infected, antibiotic-treated mice, we found (1) an altered transcriptome and defects in cell maturation, (2) a remodelled epithelium that confers resistance to intracellular bacterial colonization, and (3) changes to cyclooxygenase-2-dependent inflammation. Furthermore, in mice with a history of chronic UTI, cyclooxygenase-2-dependent inflammation allowed a variety of clinical E. coli isolates to circumvent intracellular colonization resistance and cause severe recurrent UTI, which could be prevented by cyclooxygenase-2 inhibition or vaccination. This work provides mechanistic insight into how a history of infection can impact the risk for developing recurrent infection and has implications for the development of therapeutics for recurrent UTI.

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“…Bacteriological culture approaches are limited to the quantitation of live, cultivable bacterial cells, and several species that are associated with UTI can grow in urine (Ipe et al, 2016).…”

Section: Accepted Manuscript Introductionmentioning

confidence: 99%

Quantification of bacteriuria caused by Hemolysin-positive Escherichia coli in human and mouse urine using quantitative polymerase chain reaction (qPCR) targeting hlyD

Chamoun

Sullivan

Ulett

2018

Journal of Microbiological Methods

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Uropathogenic Escherichia coli (UPEC) cause the majority of community-acquired urinary tract infections (UTIs). Quantitation of bacteriuria (the number of bacteria in urine) is important for diagnostic approaches and in diverse research applications. Most UPEC strains express hemolysin, the expression of which has been correlated with the severity of UTI in murine models of infection. In this study, we sought to develop and optimise a quantitative Polymerase Chain Reaction (qPCR) assay for enumeration of hemolysin-positive UPEC in urine. Using recombinant plasmid pJET1.2::hlyD, which we termed pGU2470, the sensitivity range and linearity of amplification of qPCR was determined using primers and a probe targeting hlyD. Whole-cell preparations containing UPEC were quantified for hlyD copy number using C values and compared to standards prepared with a known amount of pGU2470. We compared the efficiency of the assay for analysis of human and mouse urine because mouse models of human UTI are frequently used for investigating UPEC UTI. Urine samples were collected from healthy adults and mouse infection assays and used to assess any potential inhibitory effects of urine on the qPCR. The linear quantitative range of the qPCR (i.e. sensitivity) in detecting UPEC genomes was 10 copies/ml; qPCR-derived estimates of UPEC bacteriuria (based on number of genomes detected) were, on average, ten-fold higher that culture-based estimates. Finally, the frequencies of positive and negative predictions of UPEC in urine using the qPCR were equivalent to colony count methods. This assay provides an alternative to culture-based approaches for quantitation of UPEC bacteriuria in research studies.

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Urinary tract infection of mice to model human disease: Practicalities, implications and limitations

Cited by 44 publications

References 264 publications

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

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

A mucosal imprint left by prior Escherichia coli bladder infection sensitizes to recurrent disease

Quantification of bacteriuria caused by Hemolysin-positive Escherichia coli in human and mouse urine using quantitative polymerase chain reaction (qPCR) targeting hlyD

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