Evidence map›Paper›PMID 32106241›Full record

ArticlePLoS pathogens2020

The oxidative fumarase FumC is a key contributor for E. coli fitness under iron-limitation and during UTI.

Stephanie D Himpsl, Allyson E Shea, Jonathan Zora, Jolie A Stocki, Dannielle Foreman, Christopher J Alteri, Harry L T Mobley

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
4.4field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Norepinephrine derepresses the Fur regulon ofJournal of bacteriology · 2026
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  9. Emerging roles for ABC transporters as virulence factors in uropathogenicProceedings of the National Academy of Sciences of the United States of America · 2024
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  11. RpoS and the bacterial general stress response.Microbiology and molecular biology reviews : MMBR · 2024
    Review
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  14. Formate production is dispensable forInfection and immunity · 2023
    Article
  15. Molecular Typing ofJournal of pharmacy & bioallied sciences · 2023
    Article
  16. Article
  17. Transcriptomic and phenotype analysis revealed the role ofFrontiers in cellular and infection microbiology · 2023
    Article
  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Stephanie D HimpslDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.ORCID 0000-0003-2210-4161
Allyson E SheaDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.ORCID 0000-0003-1329-3888
Jonathan ZoraDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Jolie A StockiDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.ORCID 0000-0002-2597-0658
Dannielle ForemanDepartment of Natural Sciences, University of Michigan Dearborn, Dearborn, Michigan, United States of America.ORCID 0000-0002-6010-4472
Christopher J AlteriDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.ORCID 0000-0002-6367-5684
Harry L T MobleyDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
University of Michigan · USMichigan United · US

Funding

Reciprocal Control of Motility and Adherence in UTIR01AI059722 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PEARSON, MELANIE M. · 2005 to 2024
$7.4M
Vaccine to prevent E. coli urinary tract infectionR01AI116791 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MOBLEY, HARRY L. · 2016 to 2020
$2.0M
Characterization of pathogen nutrient acquisition and transport systems required during UTIF32AI147527 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SHEA, ALLYSON E · 2019 to 2022
$198k
NIAID NIH HHS F32 AI147527NIAID NIH HHS R01 AI059722NIAID NIH HHS R01 AI116791
6 · The paper itself

Abstract

The energy required for a bacterium to grow and colonize the host is generated by metabolic and respiratory functions of the cell. Proton motive force, produced by these processes, drives cellular mechanisms including redox balance, membrane potential, motility, acid resistance, and the import and export of substrates. Previously, disruption of succinate dehydrogenase (sdhB) and fumarate reductase (frdA) within the oxidative and reductive tricarboxylic acid (TCA) pathways in uropathogenic E. coli (UPEC) CFT073 indicated that the oxidative, but not the reductive TCA pathway, is required for fitness in the urinary tract. Those findings led to the hypothesis that fumA and fumC encoding fumarase enzymes of the oxidative TCA cycle would be required for UPEC colonization, while fumB of the reductive TCA pathway would be dispensable. However, only UPEC strains lacking fumC had a fitness defect during experimental urinary tract infection (UTI). To further characterize the role of respiration in UPEC during UTI, additional mutants disrupting both the oxidative and reductive TCA pathways were constructed. We found that knock-out of frdA in the sdhB mutant strain background ameliorated the fitness defect observed in the bladder and kidneys for the sdhB mutant strain and results in a fitness advantage in the bladder during experimental UTI. The fitness defect was restored in the sdhBfrdA double mutant by complementation with frdABCD. Taken together, we demonstrate that it is not the oxidative or reductive pathway that is important for UPEC fitness per se, but rather only the oxidative TCA enzyme FumC. This fumarase lacks an iron-sulfur cluster and is required for UPEC fitness during UTI, most likely acting as a counter measure against exogenous stressors, especially in the iron-limited bladder niche.

Indexed as

AnimalsCitric Acid CycleEscherichia coli InfectionsEscherichia coli ProteinsFemaleFumarate HydrataseGene Expression Regulation, BacterialIronMiceMice, Inbred CBAOxidation-ReductionOxidative StressUrinary Tract InfectionsUropathogenic Escherichia coliEscherichia coli Proteinsfumarase CFumarate HydrataseIron

Identifiers

PMID32106241
PMCPMC7064253
OpenAlexW3008910030

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.