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and Urinary Tract Infections

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  • Authors: Jessica N. Schaffer1, Melanie M. Pearson2
  • Editors: Matthew A. Mulvey3, Ann E. Stapleton4, David J. Klumpp5
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Microbiology, New York University Langone Medical Center, New York, NY 10016; 2: Department of Microbiology, New York University Langone Medical Center, New York, NY 10016; 3: University of Utah, Salt Lake City, UT; 4: University of Washington, Seattle, WA; 5: Northwestern University, Chicago, IL
    • Source: microbiolspec September 2015 vol. 3 no. 5 doi:10.1128/microbiolspec.UTI-0017-2013
  • Received 03 April 2013 Accepted 29 July 2014 Published 18 September 2015
  • Melanie M. Pearson, [email protected]
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  • Abstract:

    is a Gram-negative bacterium and is well known for its ability to robustly swarm across surfaces in a striking bulls’-eye pattern. Clinically, this organism is most frequently a pathogen of the urinary tract, particularly in patients undergoing long-term catheterization. This review covers with a focus on urinary tract infections (UTI), including disease models, vaccine development efforts, and clinical perspectives. Flagella-mediated motility, both swimming and swarming, is a central facet of this organism. The regulation of this complex process and its contribution to virulence is discussed, along with the type VI-secretion system-dependent intra-strain competition, which occurs during swarming. uses a diverse set of virulence factors to access and colonize the host urinary tract, including urease and stone formation, fimbriae and other adhesins, iron and zinc acquisition, proteases and toxins, biofilm formation, and regulation of pathogenesis. While significant advances in this field have been made, challenges remain to combatting complicated UTI and deciphering pathogenesis.

  • Citation: Schaffer J, Pearson M. 2015. and Urinary Tract Infections. Microbiol Spectrum 3(5):UTI-0017-2013. doi:10.1128/microbiolspec.UTI-0017-2013.

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/content/journal/microbiolspec/10.1128/microbiolspec.UTI-0017-2013
2015-09-18
2019-10-23

Abstract:

is a Gram-negative bacterium and is well known for its ability to robustly swarm across surfaces in a striking bulls’-eye pattern. Clinically, this organism is most frequently a pathogen of the urinary tract, particularly in patients undergoing long-term catheterization. This review covers with a focus on urinary tract infections (UTI), including disease models, vaccine development efforts, and clinical perspectives. Flagella-mediated motility, both swimming and swarming, is a central facet of this organism. The regulation of this complex process and its contribution to virulence is discussed, along with the type VI-secretion system-dependent intra-strain competition, which occurs during swarming. uses a diverse set of virulence factors to access and colonize the host urinary tract, including urease and stone formation, fimbriae and other adhesins, iron and zinc acquisition, proteases and toxins, biofilm formation, and regulation of pathogenesis. While significant advances in this field have been made, challenges remain to combatting complicated UTI and deciphering pathogenesis.

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and Urinary Tract Infections
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Citation: Schaffer J, Pearson M. 2015. and urinary tract infections. microbiolspec 3(5): doi:10.1128/microbiolspec.UTI-0017-2013
/content/microbiolspec/10.1128/microbiolspec.UTI-0017-2013.fig1
FIGURE 1
in urease-induced bladder stone. , One-quarter bladder of experimentally infected mouse (bar, 500 μm). , Higher magnification of the area indicated in panel A (bar, 100 μm). , Higher magnification of the area indicated in panel B with individual bacteria visible (bar, 5 μm). Modified from ( 32 ), with permission.
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FIGURE 1

in urease-induced bladder stone. , One-quarter bladder of experimentally infected mouse (bar, 500 μm). , Higher magnification of the area indicated in panel A (bar, 100 μm). , Higher magnification of the area indicated in panel B with individual bacteria visible (bar, 5 μm). Modified from ( 32 ), with permission.

Source: microbiolspec September 2015 vol. 3 no. 5 doi:10.1128/microbiolspec.UTI-0017-2013
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FIGURE 2
Adherence and motility genes are inversely regulated during UTI. Each line represents fold-change of a specific flagellar (left panel) or fimbrial (right panel) gene relative to mid-logarithmic phase culture . Genes in the operon are highly induced early during infection, but expression falls by 7 days post infection. Flagellar genes are initially repressed, but expression increases late in infection. Modified from ( 25 ), with permission.
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FIGURE 2

Adherence and motility genes are inversely regulated during UTI. Each line represents fold-change of a specific flagellar (left panel) or fimbrial (right panel) gene relative to mid-logarithmic phase culture . Genes in the operon are highly induced early during infection, but expression falls by 7 days post infection. Flagellar genes are initially repressed, but expression increases late in infection. Modified from ( 25 ), with permission.

Source: microbiolspec September 2015 vol. 3 no. 5 doi:10.1128/microbiolspec.UTI-0017-2013
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FIGURE 3
Swarming colony of .
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FIGURE 3

Swarming colony of .

Source: microbiolspec September 2015 vol. 3 no. 5 doi:10.1128/microbiolspec.UTI-0017-2013
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FIGURE 4
switches between swimming and swarming forms. On the left is a transmission electron micrograph (TEM) of broth-cultured, vegetative cells displaying peritrichous flagella. On the right is a TEM of differentiated swarm cells. Bundles of flagella are visible.
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FIGURE 4

switches between swimming and swarming forms. On the left is a transmission electron micrograph (TEM) of broth-cultured, vegetative cells displaying peritrichous flagella. On the right is a TEM of differentiated swarm cells. Bundles of flagella are visible.

Source: microbiolspec September 2015 vol. 3 no. 5 doi:10.1128/microbiolspec.UTI-0017-2013
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FIGURE 5
swarms across sections of latex catheter. Reproduced from ( 61 ), with permission.
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FIGURE 5

swarms across sections of latex catheter. Reproduced from ( 61 ), with permission.

Source: microbiolspec September 2015 vol. 3 no. 5 doi:10.1128/microbiolspec.UTI-0017-2013
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FIGURE 6
Expression of MR/P fimbriae is phase-variable and induced during UTI. , Immunogold electron microscopy of wild-type HI4320 labeled with gold particles targeting the MrpH tip adhesin. The cell on the left is expressing MR/P fimbriae, and the cell on the right is not (bar, 500 nm). , The amount of MR/P fimbriae present positively correlates with murine bladder colonization. Data were obtained seven days post-inoculation. Modified from ( 166 ), with permission.
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FIGURE 6

Expression of MR/P fimbriae is phase-variable and induced during UTI. , Immunogold electron microscopy of wild-type HI4320 labeled with gold particles targeting the MrpH tip adhesin. The cell on the left is expressing MR/P fimbriae, and the cell on the right is not (bar, 500 nm). , The amount of MR/P fimbriae present positively correlates with murine bladder colonization. Data were obtained seven days post-inoculation. Modified from ( 166 ), with permission.

Source: microbiolspec September 2015 vol. 3 no. 5 doi:10.1128/microbiolspec.UTI-0017-2013
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FIGURE 7
biofilm formation is MR/P-dependent. bacteria expressing GFP were grown on a cover glass in urine for 7 days. The resulting biofilm was imaged with confocal microscopy, and the 30 resulting z-stacks were stitched together to form the sagittal view. Wild-type forms thick, robust biofilms. MR/P L-ON forms dense, but thin, biofilms while MR/P L-OFF forms weak biofilms. Reprinted from ( 177 ), with permission.
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FIGURE 7

biofilm formation is MR/P-dependent. bacteria expressing GFP were grown on a cover glass in urine for 7 days. The resulting biofilm was imaged with confocal microscopy, and the 30 resulting z-stacks were stitched together to form the sagittal view. Wild-type forms thick, robust biofilms. MR/P L-ON forms dense, but thin, biofilms while MR/P L-OFF forms weak biofilms. Reprinted from ( 177 ), with permission.

Source: microbiolspec September 2015 vol. 3 no. 5 doi:10.1128/microbiolspec.UTI-0017-2013
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FIGURE 8
Overexpression of and its paralogs results in distinct phenotypes. , Swarming assays of with an empty vector or expressing or an paralog. , Gram-stained bacteria from the edge of the swarm front (bar, 50 μm). Modified from ( 162 ), with permission.
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FIGURE 8

Overexpression of and its paralogs results in distinct phenotypes. , Swarming assays of with an empty vector or expressing or an paralog. , Gram-stained bacteria from the edge of the swarm front (bar, 50 μm). Modified from ( 162 ), with permission.

Source: microbiolspec September 2015 vol. 3 no. 5 doi:10.1128/microbiolspec.UTI-0017-2013
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FIGURE 9
iron chelation is Nrp and proteobactin dependent. , agar; and , solution chrome azurol S (CAS) assays of uropathogenic CFT073 and HI4320; a color change from blue to orange indicates iron chelation. In , supernatants from log-phase cultures grown in MOPS defined media either with 0.1 mM FeCl·6HO (black bars) or without supplementation (white bars) were concentrated 50-fold before being used in a liquid CAS assay ( supernatants were not concentrated). Single and mutants are not impaired in iron chelation, but the double mutant is. Reprinted from ( 238 ), with permission.
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FIGURE 9

iron chelation is Nrp and proteobactin dependent. , agar; and , solution chrome azurol S (CAS) assays of uropathogenic CFT073 and HI4320; a color change from blue to orange indicates iron chelation. In , supernatants from log-phase cultures grown in MOPS defined media either with 0.1 mM FeCl·6HO (black bars) or without supplementation (white bars) were concentrated 50-fold before being used in a liquid CAS assay ( supernatants were not concentrated). Single and mutants are not impaired in iron chelation, but the double mutant is. Reprinted from ( 238 ), with permission.

Source: microbiolspec September 2015 vol. 3 no. 5 doi:10.1128/microbiolspec.UTI-0017-2013
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Tables

and Urinary Tract Infections
[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/microbiolspec/10.1128/microbiolspec.UTI-0017-2013-1,webId=/content/author/microbiolspec/10.1128/microbiolspec.UTI-0017-2013-1,properties={foaf_givenname=Jessica N., foaf_name=Jessica N. Schaffer, foaf_surname=Schaffer, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.UTI-0017-2013-aff1]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/microbiolspec/10.1128/microbiolspec.UTI-0017-2013-2,webId=/content/author/microbiolspec/10.1128/microbiolspec.UTI-0017-2013-2,properties={foaf_givenname=Melanie M., foaf_name=Melanie M. Pearson, foaf_surname=Pearson, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.UTI-0017-2013-aff2]]}]]
Citation: Schaffer J, Pearson M. 2015. and urinary tract infections. microbiolspec 3(5): doi:10.1128/microbiolspec.UTI-0017-2013
/content/microbiolspec/10.1128/microbiolspec.UTI-0017-2013.T1
TABLE 1
Genes that contribute to swarming in
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TABLE 1

Genes that contribute to swarming in

Source: microbiolspec September 2015 vol. 3 no. 5 doi:10.1128/microbiolspec.UTI-0017-2013
/content/microbiolspec/10.1128/microbiolspec.UTI-0017-2013.T2
TABLE 2
The fimbriae of . The name, genomic location, Greek classification, determination of virulence, and MrpJ homolog of each fimbrial operon in
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TABLE 2

The fimbriae of . The name, genomic location, Greek classification, determination of virulence, and MrpJ homolog of each fimbrial operon in

Source: microbiolspec September 2015 vol. 3 no. 5 doi:10.1128/microbiolspec.UTI-0017-2013
/content/microbiolspec/10.1128/microbiolspec.UTI-0017-2013.T3
TABLE 3
Iron-related genes in . Iron-related genes from were identified by homology to other iron-related genes. Genes identified as iron-related by homology but not identified using one of the four conditions shown were excluded. A checkmark indicates that one or more of the genes in the row were identified using the condition specified
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TABLE 3

Iron-related genes in . Iron-related genes from were identified by homology to other iron-related genes. Genes identified as iron-related by homology but not identified using one of the four conditions shown were excluded. A checkmark indicates that one or more of the genes in the row were identified using the condition specified

Source: microbiolspec September 2015 vol. 3 no. 5 doi:10.1128/microbiolspec.UTI-0017-2013

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