Rapid Growth of Uropathogenic <italic toggle="yes">Escherichia coli</italic> during Human Urinary Tract Infection

ABSTRACT Uropathogenic Escherichia coli (UPEC) strains cause most uncomplicated urinary tract infections (UTIs). These strains are a subgroup of extraintestinal pathogenic E. coli (ExPEC) strains that infect extraintestinal sites, including urinary tract, meninges, bloodstream, lungs, and surgical s...

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Autores principales: Valerie S. Forsyth, Chelsie E. Armbruster, Sara N. Smith, Ali Pirani, A. Cody Springman, Matthew S. Walters, Greta R. Nielubowicz, Stephanie D. Himpsl, Evan S. Snitkin, Harry L. T. Mobley
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Publicado: American Society for Microbiology 2018
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ABU
PTR
UTI
Acceso en línea:https://doaj.org/article/1a994712044b48a2b02cce9b0de39065
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spelling oai:doaj.org-article:1a994712044b48a2b02cce9b0de390652021-11-15T15:53:26ZRapid Growth of Uropathogenic <italic toggle="yes">Escherichia coli</italic> during Human Urinary Tract Infection10.1128/mBio.00186-182150-7511https://doaj.org/article/1a994712044b48a2b02cce9b0de390652018-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00186-18https://doaj.org/toc/2150-7511ABSTRACT Uropathogenic Escherichia coli (UPEC) strains cause most uncomplicated urinary tract infections (UTIs). These strains are a subgroup of extraintestinal pathogenic E. coli (ExPEC) strains that infect extraintestinal sites, including urinary tract, meninges, bloodstream, lungs, and surgical sites. Here, we hypothesize that UPEC isolates adapt to and grow more rapidly within the urinary tract than other E. coli isolates and survive in that niche. To date, there has not been a reliable method available to measure their growth rate in vivo. Here we used two methods: segregation of nonreplicating plasmid pGTR902, and peak-to-trough ratio (PTR), a sequencing-based method that enumerates bacterial chromosomal replication forks present during cell division. In the murine model of UTI, UPEC strain growth was robust in vivo, matching or exceeding in vitro growth rates and only slowing after reaching high CFU counts at 24 and 30 h postinoculation (hpi). In contrast, asymptomatic bacteriuria (ABU) strains tended to maintain high growth rates in vivo at 6, 24, and 30 hpi, and population densities did not increase, suggesting that host responses or elimination limited population growth. Fecal strains displayed moderate growth rates at 6 hpi but did not survive to later times. By PTR, E. coli in urine of human patients with UTIs displayed extraordinarily rapid growth during active infection, with a mean doubling time of 22.4 min. Thus, in addition to traditional virulence determinants, including adhesins, toxins, iron acquisition, and motility, very high growth rates in vivo and resistance to the innate immune response appear to be critical phenotypes of UPEC strains. IMPORTANCE Uropathogenic Escherichia coli (UPEC) strains cause most urinary tract infections in otherwise healthy women. While we understand numerous virulence factors are utilized by E. coli to colonize and persist within the urinary tract, these properties are inconsequential unless bacteria can divide rapidly and survive the host immune response. To determine the contribution of growth rate to successful colonization and persistence, we employed two methods: one involving the segregation of a nonreplicating plasmid in bacteria as they divide and the peak-to-trough ratio, a sequencing-based method that enumerates chromosomal replication forks present during cell division. We found that UPEC strains divide extraordinarily rapidly during human UTIs. These techniques will be broadly applicable to measure in vivo growth rates of other bacterial pathogens during host colonization.Valerie S. ForsythChelsie E. ArmbrusterSara N. SmithAli PiraniA. Cody SpringmanMatthew S. WaltersGreta R. NielubowiczStephanie D. HimpslEvan S. SnitkinHarry L. T. MobleyAmerican Society for MicrobiologyarticleABUExPECPTRUPECUTIin vivo growthMicrobiologyQR1-502ENmBio, Vol 9, Iss 2 (2018)
institution DOAJ
collection DOAJ
language EN
topic ABU
ExPEC
PTR
UPEC
UTI
in vivo growth
Microbiology
QR1-502
spellingShingle ABU
ExPEC
PTR
UPEC
UTI
in vivo growth
Microbiology
QR1-502
Valerie S. Forsyth
Chelsie E. Armbruster
Sara N. Smith
Ali Pirani
A. Cody Springman
Matthew S. Walters
Greta R. Nielubowicz
Stephanie D. Himpsl
Evan S. Snitkin
Harry L. T. Mobley
Rapid Growth of Uropathogenic <italic toggle="yes">Escherichia coli</italic> during Human Urinary Tract Infection
description ABSTRACT Uropathogenic Escherichia coli (UPEC) strains cause most uncomplicated urinary tract infections (UTIs). These strains are a subgroup of extraintestinal pathogenic E. coli (ExPEC) strains that infect extraintestinal sites, including urinary tract, meninges, bloodstream, lungs, and surgical sites. Here, we hypothesize that UPEC isolates adapt to and grow more rapidly within the urinary tract than other E. coli isolates and survive in that niche. To date, there has not been a reliable method available to measure their growth rate in vivo. Here we used two methods: segregation of nonreplicating plasmid pGTR902, and peak-to-trough ratio (PTR), a sequencing-based method that enumerates bacterial chromosomal replication forks present during cell division. In the murine model of UTI, UPEC strain growth was robust in vivo, matching or exceeding in vitro growth rates and only slowing after reaching high CFU counts at 24 and 30 h postinoculation (hpi). In contrast, asymptomatic bacteriuria (ABU) strains tended to maintain high growth rates in vivo at 6, 24, and 30 hpi, and population densities did not increase, suggesting that host responses or elimination limited population growth. Fecal strains displayed moderate growth rates at 6 hpi but did not survive to later times. By PTR, E. coli in urine of human patients with UTIs displayed extraordinarily rapid growth during active infection, with a mean doubling time of 22.4 min. Thus, in addition to traditional virulence determinants, including adhesins, toxins, iron acquisition, and motility, very high growth rates in vivo and resistance to the innate immune response appear to be critical phenotypes of UPEC strains. IMPORTANCE Uropathogenic Escherichia coli (UPEC) strains cause most urinary tract infections in otherwise healthy women. While we understand numerous virulence factors are utilized by E. coli to colonize and persist within the urinary tract, these properties are inconsequential unless bacteria can divide rapidly and survive the host immune response. To determine the contribution of growth rate to successful colonization and persistence, we employed two methods: one involving the segregation of a nonreplicating plasmid in bacteria as they divide and the peak-to-trough ratio, a sequencing-based method that enumerates chromosomal replication forks present during cell division. We found that UPEC strains divide extraordinarily rapidly during human UTIs. These techniques will be broadly applicable to measure in vivo growth rates of other bacterial pathogens during host colonization.
format article
author Valerie S. Forsyth
Chelsie E. Armbruster
Sara N. Smith
Ali Pirani
A. Cody Springman
Matthew S. Walters
Greta R. Nielubowicz
Stephanie D. Himpsl
Evan S. Snitkin
Harry L. T. Mobley
author_facet Valerie S. Forsyth
Chelsie E. Armbruster
Sara N. Smith
Ali Pirani
A. Cody Springman
Matthew S. Walters
Greta R. Nielubowicz
Stephanie D. Himpsl
Evan S. Snitkin
Harry L. T. Mobley
author_sort Valerie S. Forsyth
title Rapid Growth of Uropathogenic <italic toggle="yes">Escherichia coli</italic> during Human Urinary Tract Infection
title_short Rapid Growth of Uropathogenic <italic toggle="yes">Escherichia coli</italic> during Human Urinary Tract Infection
title_full Rapid Growth of Uropathogenic <italic toggle="yes">Escherichia coli</italic> during Human Urinary Tract Infection
title_fullStr Rapid Growth of Uropathogenic <italic toggle="yes">Escherichia coli</italic> during Human Urinary Tract Infection
title_full_unstemmed Rapid Growth of Uropathogenic <italic toggle="yes">Escherichia coli</italic> during Human Urinary Tract Infection
title_sort rapid growth of uropathogenic <italic toggle="yes">escherichia coli</italic> during human urinary tract infection
publisher American Society for Microbiology
publishDate 2018
url https://doaj.org/article/1a994712044b48a2b02cce9b0de39065
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