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A murine model of urinary tract infection

Nature Protocols volume 4, pages 1230–1243 (2009)Cite this article

Abstract

Urinary tract infections (UTIs) inflict extreme pain and discomfort to those affected and have profound medical and socioeconomic impact. Although acute UTIs are often treatable with antibiotics, a large proportion of patients suffer from multiple recurrent infections. Here, we describe and provide a protocol for a robust murine UTI model that allows for the study of uropathogens in an ideal setting. The infections in the urinary tract can be monitored quantitatively by determining the bacterial loads at different times post-infection. In addition, the simple bladder architecture allows observation of disease progression and the uropathogenic virulence cascade using a variety of microscopic techniques. This mouse UTI model is extremely flexible, allowing the study of different bacterial strains and species of uropathogens in a broad range of mouse genetic backgrounds. We have used this protocol to identify important aspects of the host-pathogen interaction that determine the outcome of infection. The time required to complete the entire procedure will depend on the number of bacterial strains and mice included in the study. Nevertheless, one should expect 4 h of hands-on time, including inoculum preparation on the day of infection, transurethral inoculation, tissue harvest and post-harvest processing for a small group of mice (e.g., 5 mice).

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Figure 1: Mouse urothelium.
Figure 2: Schematic of the pap and fim operons.
Figure 3: Uropathogenic Escherichia coli (UPEC) pathogenic cycle.
Figure 4: The intracellular bacterial community (IBC).
Figure 5: Typical make-up of a mobile induction system.
Figure 6: Urinary catheter.
Figure 7: Catheterization process.
Figure 8: Mouse urinary-tract anatomy.
Figure 9: Stretched bladder on silicone pad.
Figure 10: Sample tissue bacterial titers.
Figure 11: Confocal fluorescence microscopy images of intracellular bacterial communities (IBCs) and filamentous bacteria.
Figure 12: Histological images of infected bladder.

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Acknowledgements

We thank all current and former Hultgren lab members in optimizing and perfecting the murine UTI model. We thank Dr. Wandy Beatty in the Molecular Microbiology Imaging Facility at Washington University School of Medicine for her excellent technical assistance with fluorescence microscopy. C.-S.H., K.W.D. and S.J.H. are supported by National Institutes of Health Office of Research on Women's Health: Specialized Center of Research on Sex and Gender Factors Affecting Women's Health, grant R01 DK64540, National Institute of Diabetes and Digestive and Kidney Diseases, grants R01 DK051406 and National Institute of Allergy and Infectious Diseases, grants R01 AI29549, R01 AI48689 and R01 AI50011.

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Authors and Affiliations

  1. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA

    Chia-Suei Hung, Karen W Dodson & Scott J Hultgren

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  1. Chia-Suei Hung
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Contributions

C.-S.H., K.W.D. and S.J.H. wrote the manuscript. C.-S.H. generated the sample data presented in Anticipated Results.

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Correspondence to Scott J Hultgren.

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Hung, CS., Dodson, K. & Hultgren, S. A murine model of urinary tract infection. Nat Protoc 4, 1230–1243 (2009). https://doi.org/10.1038/nprot.2009.116

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