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Invasion of Host Cells and Tissues by Uropathogenic Bacteria

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  • Authors: Adam J. Lewis1, Amanda C. Richards2, Matthew A. Mulvey3
  • Editors: Matthew A. Mulvey4, Ann E. Stapleton5, David J. Klumpp6
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, UT 84112; 2: Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, UT 84112; 3: Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, UT 84112; 4: University of Utah, Salt Lake City, UT; 5: University of Washington, Seattle, WA; 6: Northwestern University, Chicago, IL
    • Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.UTI-0026-2016
  • Received 21 September 2016 Accepted 21 November 2016 Published 16 December 2016
  • Matthew A. Mulvey, [email protected]
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  • Abstract:

    Within the mammalian urinary tract uropathogenic bacteria face many challenges, including the shearing flow of urine, numerous antibacterial molecules, the bactericidal effects of phagocytes, and a scarcity of nutrients. These problems may be circumvented in part by the ability of uropathogenic and several other uropathogens to invade the epithelial cells that line the urinary tract. By entering host cells, uropathogens can gain access to additional nutrients and protection from both host defenses and antibiotic treatments. Translocation through host cells can facilitate bacterial dissemination within the urinary tract, while the establishment of stable intracellular bacterial populations may create reservoirs for relapsing and chronic urinary tract infections. Here we review the mechanisms and consequences of host cell invasion by uropathogenic bacteria, with consideration of the defenses that are brought to bear against facultative intracellular pathogens within the urinary tract. The relevance of host cell invasion to the pathogenesis of urinary tract infections in human patients is also assessed, along with some of the emerging treatment options that build upon our growing understanding of the infectious life cycle of uropathogenic and other uropathogens.

  • Citation: Lewis A, Richards A, Mulvey M. 2016. Invasion of Host Cells and Tissues by Uropathogenic Bacteria. Microbiol Spectrum 4(6):UTI-0026-2016. doi:10.1128/microbiolspec.UTI-0026-2016.

Key Concept Ranking

Infection and Immunity
0.62435114
Type 1 Pili
0.59056365
Outer Membrane Proteins
0.49387258
Urinary Tract Infections
0.459103
Transmission Electron Microscopy
0.45485198
0.62435114

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/content/journal/microbiolspec/10.1128/microbiolspec.UTI-0026-2016
2016-12-16
2019-10-14

Abstract:

Within the mammalian urinary tract uropathogenic bacteria face many challenges, including the shearing flow of urine, numerous antibacterial molecules, the bactericidal effects of phagocytes, and a scarcity of nutrients. These problems may be circumvented in part by the ability of uropathogenic and several other uropathogens to invade the epithelial cells that line the urinary tract. By entering host cells, uropathogens can gain access to additional nutrients and protection from both host defenses and antibiotic treatments. Translocation through host cells can facilitate bacterial dissemination within the urinary tract, while the establishment of stable intracellular bacterial populations may create reservoirs for relapsing and chronic urinary tract infections. Here we review the mechanisms and consequences of host cell invasion by uropathogenic bacteria, with consideration of the defenses that are brought to bear against facultative intracellular pathogens within the urinary tract. The relevance of host cell invasion to the pathogenesis of urinary tract infections in human patients is also assessed, along with some of the emerging treatment options that build upon our growing understanding of the infectious life cycle of uropathogenic and other uropathogens.

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Invasion of Host Cells and Tissues by Uropathogenic Bacteria
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Citation: Lewis A, Richards A, Mulvey M. 2016. Invasion of host cells and tissues by uropathogenic bacteria. microbiolspec 4(6): doi:10.1128/microbiolspec.UTI-0026-2016
/content/microbiolspec/10.1128/microbiolspec.UTI-0026-2016.fig1
FIGURE 1

Type 1 pili mediate UPEC entry into bladder epithelial cells. High-resolution deep-etch electron microscopy image showing UPEC (yellow) bound to a mouse bladder umbrella cell (blue) via multiple type 1 pili. Close-up view of a type 1 pilus, showing the 3-nm-wide FimH-containing tip fibrillum structure (arrowhead). Close-up view of the 16-nm-wide hexagonal uroplakin complexes that are embedded within the umbrella cell asymmetric unit membrane (AUM). High-resolution freeze-fracture/deep-etch electron microscopy images showing the AUM enveloping bound UPEC. Scale bars = 0.5 μm. Images are reprinted from ( 18 ) and ( 9 ) with permission of the publishers.

microbiolspec/4/6/UTI-0026-2016-fig1_thmb.gif
microbiolspec/4/6/UTI-0026-2016-fig1.gif
Image of FIGURE 1
FIGURE 1

Type 1 pili mediate UPEC entry into bladder epithelial cells. High-resolution deep-etch electron microscopy image showing UPEC (yellow) bound to a mouse bladder umbrella cell (blue) via multiple type 1 pili. Close-up view of a type 1 pilus, showing the 3-nm-wide FimH-containing tip fibrillum structure (arrowhead). Close-up view of the 16-nm-wide hexagonal uroplakin complexes that are embedded within the umbrella cell asymmetric unit membrane (AUM). High-resolution freeze-fracture/deep-etch electron microscopy images showing the AUM enveloping bound UPEC. Scale bars = 0.5 μm. Images are reprinted from ( 18 ) and ( 9 ) with permission of the publishers.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.UTI-0026-2016
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FIGURE 2

Localization of UPEC within the bladder urothelium. Confocal images of tissue sections from infected mouse bladders show IBCs (green) within umbrella cells (UC). F-actin (red) is sparse within these host cells but dense within the underlying immature cells (IC). A single bacterium, localized within a LAMP-1-positive compartment (blue) and surrounded by F-actin, is visible within one of the immature cells (box). Images show magnified views of the area that is boxed in (B). Figures are reprinted from ( 26 ) with permission of the publisher.

microbiolspec/4/6/UTI-0026-2016-fig2_thmb.gif
microbiolspec/4/6/UTI-0026-2016-fig2.gif
Image of FIGURE 2
FIGURE 2

Localization of UPEC within the bladder urothelium. Confocal images of tissue sections from infected mouse bladders show IBCs (green) within umbrella cells (UC). F-actin (red) is sparse within these host cells but dense within the underlying immature cells (IC). A single bacterium, localized within a LAMP-1-positive compartment (blue) and surrounded by F-actin, is visible within one of the immature cells (box). Images show magnified views of the area that is boxed in (B). Figures are reprinted from ( 26 ) with permission of the publisher.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.UTI-0026-2016
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/content/microbiolspec/10.1128/microbiolspec.UTI-0026-2016.fig3
FIGURE 3

The efflux and filamentation of UPEC coincident with the exfoliation of IBC-containing umbrella cells. Scanning electron microscopy images show filamentous forms of UPEC, as well as their normal-sized counterparts, emerging from within IBCs. Image from a hematoxylin- and eosin-stained bladder section highlights the ability of filamentous UPEC forms to extend long distances through umbrella cells. Confocal image shows an IBC (blue) in close association with cytokeratin intermediate filaments (green) within an umbrella cell that is undergoing exfoliation. LAMP-1-positive compartments are red. Scale bars = 5 μm (A–C); 10 μm (D, E). Images are from mouse bladders recovered 6 hours after transurethral inoculation with UPEC. The figures are modified from ( 26 ) or reprinted from ( 17 ) with permission of the publishers.

microbiolspec/4/6/UTI-0026-2016-fig3_thmb.gif
microbiolspec/4/6/UTI-0026-2016-fig3.gif
Image of FIGURE 3
FIGURE 3

The efflux and filamentation of UPEC coincident with the exfoliation of IBC-containing umbrella cells. Scanning electron microscopy images show filamentous forms of UPEC, as well as their normal-sized counterparts, emerging from within IBCs. Image from a hematoxylin- and eosin-stained bladder section highlights the ability of filamentous UPEC forms to extend long distances through umbrella cells. Confocal image shows an IBC (blue) in close association with cytokeratin intermediate filaments (green) within an umbrella cell that is undergoing exfoliation. LAMP-1-positive compartments are red. Scale bars = 5 μm (A–C); 10 μm (D, E). Images are from mouse bladders recovered 6 hours after transurethral inoculation with UPEC. The figures are modified from ( 26 ) or reprinted from ( 17 ) with permission of the publishers.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.UTI-0026-2016
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FIGURE 4

UPEC invasion of bladder epithelial cells. Model depicts host and bacterial factors that have been identified as regulators of bladder cell invasion by UPEC. Potential therapeutics are also indicated. The host factors that can modulate the FimH-dependent entry of UPEC into bladder cells are interconnected. The image in (B) was created using the STRING database (version 10.0) of known and predicted protein-protein interactions ( 198 ). Line thickness indicates the strength of the supporting data.

microbiolspec/4/6/UTI-0026-2016-fig4_thmb.gif
microbiolspec/4/6/UTI-0026-2016-fig4.gif
Image of FIGURE 4
FIGURE 4

UPEC invasion of bladder epithelial cells. Model depicts host and bacterial factors that have been identified as regulators of bladder cell invasion by UPEC. Potential therapeutics are also indicated. The host factors that can modulate the FimH-dependent entry of UPEC into bladder cells are interconnected. The image in (B) was created using the STRING database (version 10.0) of known and predicted protein-protein interactions ( 198 ). Line thickness indicates the strength of the supporting data.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.UTI-0026-2016
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/content/microbiolspec/10.1128/microbiolspec.UTI-0026-2016.fig5
FIGURE 5

The fates of UPEC following entry into bladder epithelial cells. See text for details.

microbiolspec/4/6/UTI-0026-2016-fig5_thmb.gif
microbiolspec/4/6/UTI-0026-2016-fig5.gif
Image of FIGURE 5
FIGURE 5

The fates of UPEC following entry into bladder epithelial cells. See text for details.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.UTI-0026-2016
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