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Urinary tract infections: pathogenesis, host susceptibility and emerging therapeutics

Nature Reviews Microbiology (2024)Cite this article

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Abstract

Urinary tract infections (UTIs), which include any infection of the urethra, bladder or kidneys, account for an estimated 400 million infections and billions of dollars in health-care spending per year. The most common bacterium implicated in UTI is uropathogenic Escherichia coli, but diverse pathogens including Klebsiella, Enterococcus, Pseudomonas, Staphylococcus and even yeast such as Candida species can also cause UTIs. UTIs occur in both women and men and in both healthy and immunocompromised patients. However, certain patient factors predispose to disease: for example, female sex, history of prior UTI, or the presence of a urinary catheter or other urinary tract abnormality. The current clinical paradigm for the treatment of UTIs involves the use of antibiotics. Unfortunately, the efficacy of this approach is dwindling as the prevalence of antimicrobial resistance rises among UTI isolates, and the immense quantity of antibiotics prescribed annually for these infections contributes to the emergence of resistant pathogens. Therefore, there is an urgent need for new antibiotics and non-antibiotic treatment and prevention strategies. In this Review, we discuss how recent studies of bacterial pathogenesis, recurrence, persistence, host–pathogen interactions and host susceptibility factors have elucidated new and promising targets for the treatment and prevention of UTIs.

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Fig. 1: Epidemiology of UTIs.
Fig. 2: Pathogenesis of urinary tract infections.
Fig. 3: Model of the gut–vagina–bladder axis.
Fig. 4: Model for bladder epithelial stem cell remodelling and trained immunity.

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Acknowledgements

The authors thank K. W. Dodson for editorial assistance and helpful suggestions on the manuscript. The work in the laboratory of the authors was supported by grants AI157797, AI029549 and AI048689 from the US National Institution of Allergy and Infectious Diseases and by grants DK132327 and DK121822 from the US National Institute of Diabetes and Digestive and Kidney Diseases. M.R.T. was supported by F30DK135390 and S.K.R. was supported by T32DK077653 from the US National Institute of Diabetes and Digestive and Kidney Diseases. The authors apologize to researchers whose work was not included in this Review owing to space constraints.

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  1. These authors contributed equally: Morgan R. Timm, Seongmi K. Russell.

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

    Morgan R. Timm & Scott J. Hultgren

  2. Center for Women’s Infectious Disease Research, Washington University School of Medicine, St. Louis, MO, USA

    Morgan R. Timm & Scott J. Hultgren

  3. Department of Paediatrics, Washington University School of Medicine, St. Louis, MO, USA

    Seongmi K. Russell

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Competing interests

S.J.H. has an ownership interest in Fimbrion Therapeutics and may benefit if the company is successful in marketing mannosides. S.J.H. is also the chief scientific officer of QureTech Bio. S.J.H. is an inventor on multiple patents pertaining to urinary tract infection therapeutics including the FimCH and EbpA vaccines. M.R.T. and S.J.H are inventors on a patent for the Abp2D vaccine. S.K.R. declares no competing interests.

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Timm, M.R., Russell, S.K. & Hultgren, S.J. Urinary tract infections: pathogenesis, host susceptibility and emerging therapeutics. Nat Rev Microbiol (2024). https://doi.org/10.1038/s41579-024-01092-4

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