Bacteriophages of the lower urinary tract

Abstract

The discovery of bacteria in the female urinary bladder has fundamentally changed current dogma regarding the urinary tract and related urinary disorders. Previous research characterized many of the bacterial components of the female urinary tract, but the viral fraction of this community is largely unknown. Viruses within the human microbiota far outnumber bacterial cells, with the most abundant viruses being those that infect bacteria (bacteriophages). Similar to observations within the microbiota of the gut and oral cavity, preliminary surveys of the urinary tract and bladder microbiota indicate a rich diversity of uncharacterized bacteriophage (phage) species. Phages are vital members of the microbiota, having critical roles in shaping bacterial metabolism and community structure. Although phages have been discovered in the urinary tract, such as phages that infect Escherichia coli, sampling them is challenging owing to low biomass, possible contamination when using non-invasive methods and the invasiveness of methods that reduce the potential for contamination. Phages could influence bladder health, but an understanding of the association between phage communities, bacterial populations and bladder health is in its infancy. However, evidence suggests that phages can defend the host against pathogenic bacteria and, therefore, modulation of the microbiome using phages has therapeutic potential for lower urinary tract symptoms. Furthermore, as natural predators of bacteria, phages have garnered renewed interest for their use as antimicrobial agents, for instance, in the treatment of urinary tract infections.

Key points

  • Bacteriophages (phages) are abundant members of the microbiota of the lower urinary tract.

  • Active or lytic phages have been isolated from urine samples, but the majority of phages within the urinary microbiota persist through dormant infections, the lysogenic life cycle.

  • Evidence suggests that phages have a role in modulating the composition of the urinary microbiota, similar to that observed in microbiota of other organs of the human body.

  • Phage therapy, or the use of phages to treat pathogenic bacterial infections, is an active area of research within urology given their potential use to treat urinary tract infections.

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Fig. 1: Lytic and lysogenic cycles of phages and their impact on microbiota.
Fig. 2: The process of transduction.
Fig. 3: Phage tail morphologies.
Fig. 4: Bacteriophage Greed, isolated from catheterized urine microbiome sample.

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Acknowledgements

This work was supported by the NIH (R01 DK104718 to A.J.W.). A.G. is supported by the Carbon Research Fellowship at Loyola University Chicago. T.M.-E. was supported by a Loyola University Chicago Interdisciplinary Research Fellowship. The authors thank J. Shapiro for critical reading of the manuscript and assistance with generating the transmission electron microscopy image.

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Nature Reviews Urology thanks A. Górski and other anonymous reviewer(s) for their contribution to the peer review of this work.

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A.G. and T.M.-E. researched data for the article. All authors made substantial contribution to discussion of content, wrote the article and reviewed and edited the manuscript before submission.

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Correspondence to Catherine Putonti.

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Garretto, A., Miller-Ensminger, T., Wolfe, A.J. et al. Bacteriophages of the lower urinary tract. Nat Rev Urol 16, 422–432 (2019). https://doi.org/10.1038/s41585-019-0192-4

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