Host–pathogen checkpoints and population bottlenecks in persistent and intracellular uropathogenic Escherichia coli bladder infection

Authors

  • Thomas J. Hannan,

    1. Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA
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  • Makrina Totsika,

    1. Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Qld, Australia
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  • Kylie J. Mansfield,

    1. Graduate School of Medicine, University of Wollongong, Wollongong, NSW, Australia
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  • Kate H. Moore,

    1. Department of Urogynaecology, The St George Hospital, University of New South Wales, Kogarah, NSW, Australia
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  • Mark A. Schembri,

    1. Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Qld, Australia
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  • Scott J. Hultgren

    Corresponding author
    1. Department of Molecular Microbiology, Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO, USA
    • Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA
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Correspondence: Scott J. Hultgren, Department of Molecular Microbiology, Center for Women's Infectious Disease Research, Washington University School of Medicine, Campus Box 8230, 660 South Euclid Avenue, St. Louis, MO 63110, USA. Tel.: +1 314 362 6772; fax: +1 314 362 1998; e-mail: hultgren@borcim.wustl.edu

Abstract

Bladder infections affect millions of people yearly, and recurrent symptomatic infections (cystitis) are very common. The rapid increase in infections caused by multidrug-resistant uropathogens threatens to make recurrent cystitis an increasingly troubling public health concern. Uropathogenic Escherichia coli (UPEC) cause the vast majority of bladder infections. Upon entry into the lower urinary tract, UPEC face obstacles to colonization that constitute population bottlenecks, reducing diversity, and selecting for fit clones. A critical mucosal barrier to bladder infection is the epithelium (urothelium). UPEC bypass this barrier when they invade urothelial cells and form intracellular bacterial communities (IBCs), a process which requires type 1 pili. IBCs are transient in nature, occurring primarily during acute infection. Chronic bladder infection is common and can be either latent, in the form of the quiescent intracellular reservoir (QIR), or active, in the form of asymptomatic bacteriuria (ASB/ABU) or chronic cystitis. In mice, the fate of bladder infection, QIR, ASB, or chronic cystitis, is determined within the first 24 h of infection and constitutes a putative host–pathogen mucosal checkpoint that contributes to susceptibility to recurrent cystitis. Knowledge of these checkpoints and bottlenecks is critical for our understanding of bladder infection and efforts to devise novel therapeutic strategies.

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