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  • Review Article
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Host–pathogen interactions in urinary tract infection

Nature Reviews Urology volume 7, pages 430–441 (2010)Cite this article

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Abstract

The urinary tract is a common site of bacterial infections; nearly half of all women experience at least one urinary tract infection (UTI) during their lifetime. These infections are classified based on the condition of the host. Uncomplicated infections affect otherwise healthy individuals and are most commonly caused by uropathogenic Escherichia coli, whereas complicated infections affect patients with underlying difficulties, such as a urinary tract abnormality or catheterization, and are commonly caused by species such as Proteus mirabilis. Virulence and fitness factors produced by both pathogens include fimbriae, toxins, flagella, iron acquisition systems, and proteins that function in immune evasion. Additional factors that contribute to infection include the formation of intracellular bacterial communities by E. coli and the production of urease by P. mirabilis, which can result in urinary stone formation. Innate immune responses are induced or mediated by pattern recognition receptors, antimicrobial peptides, and neutrophils. The adaptive immune response to UTI is less well understood. Host factors TLR4 and CXCR1 are implicated in disease outcome and susceptibility, respectively. Low levels of TLR4 are associated with asymptomatic bacteriuria while low levels of CXCR1 are associated with increased incidence of acute pyelonephritis. Current research is focused on the identification of additional virulence factors and therapeutic or prophylactic targets that might be used in the generation of vaccines against both uropathogens.

Key Points

  • The urinary tract is a common site of bacterial infection

  • Uropathogenic Escherichia coli and Proteus mirabilis are representative pathogens of uncomplicated and complicated urinary tract infection (UTI), respectively

  • Virulence and fitness factors synthesized by both pathogens include fimbriae, toxins, flagella, iron acquisition systems, and proteins that function in immune evasion

  • Additional factors that contribute to infection include the formation of intracellular bacterial communities by E. coli and the production of urease by P. mirabilis, which can result in urinary stone formation

  • Innate immune responses are induced or mediated by pattern recognition receptors, antimicrobial peptides, and neutrophils; the adaptive immune response to UTI is less well understood

  • Host factors TLR4 and CXCR1 are implicated in disease outcome and susceptibility, respectively; low levels of TLR4 are associated with asymptomatic bacteriuria; low levels of CXCR1 are associated with increased incidence of acute pyelonephritis

  • Reverse vaccinology approaches are currently underway to identify potential vaccine candidates for both pathogens

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Figure 1: Overview of uropathogen virulence factors.
Figure 2: Known mechanisms of immune evasion.
Figure 3: Formation of urinary stones is the result of bacterial urease.
Figure 4: Uropathogenic Escherichia coli interaction with components of the host immune system.

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Acknowledgements

We sincerely apologize to authors whose important work could not be included in this article owing to space limitations. We would like to thank Erin Hagan, Melanie Pearson, Patrick Vigil, and Kelsey Sivick for thoughtful discussions. This work was supported in part by Public Health Service Grants AI43363 and AI059722 from the National Institutes of Health.

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  1. Department of Microbiology and Immunology, University of Michigan Medical School, 5641 Medical Science Building II, 1150 West Medical Center Drive, Ann Arbor, 48109-0620, MI, USA

    Greta R. Nielubowicz & Harry L. T. Mobley

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Nielubowicz, G., Mobley, H. Host–pathogen interactions in urinary tract infection. Nat Rev Urol 7, 430–441 (2010). https://doi.org/10.1038/nrurol.2010.101

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