Evidence map›Paper›PMID 28614382›Full record

ArticlePLoS pathogens2017

Genome-wide transposon mutagenesis of Proteus mirabilis: Essential genes, fitness factors for catheter-associated urinary tract infection, and the impact of polymicrobial infection on fitness requirements.

Chelsie E Armbruster, Valerie Forsyth-DeOrnellas, Alexandra O Johnson, Sara N Smith, Lili Zhao, Weisheng Wu, Harry L T Mobley

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
4.7field-weighted citation impact, top 3% 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

71 citing papers in PubMed, 123 citations in OpenAlex.

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11 more citing papers are in PubMed but not listed here.

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 1 institution in 1 country.

Chelsie E ArmbrusterDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.ORCID http://orcid.org/0000-0002-2165-2759
Valerie Forsyth-DeOrnellasDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Alexandra O JohnsonDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.ORCID http://orcid.org/0000-0003-3567-2176
Sara N SmithDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Lili ZhaoDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, United States of America.
Weisheng WuDepartment of Computational Medicine & Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Harry L T MobleyDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.ORCID http://orcid.org/0000-0001-9195-7665
University of Michigan · 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
Pathogenesis of Polymicrobial Catheter-Associated Urinary Tract InfectionR00DK105205 · NIDDK · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI ARMBRUSTER, CHELSIE ELIZABETH · 2018 to 2020
$727k
Pathogenesis of polymicrobial catheter-associated urinary tract infectionK99DK105205 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ARMBRUSTER, CHELSIE ELIZABETH · 2015 to 2016
$182k
NIAID NIH HHS R01 AI059722NIDDK NIH HHS K99 DK105205NIDDK NIH HHS R00 DK105205
6 · The paper itself

Abstract

The Gram-negative bacterium Proteus mirabilis is a leading cause of catheter-associated urinary tract infections (CAUTIs), which are often polymicrobial. Numerous prior studies have uncovered virulence factors for P. mirabilis pathogenicity in a murine model of ascending UTI, but little is known concerning pathogenesis during CAUTI or polymicrobial infection. In this study, we utilized five pools of 10,000 transposon mutants each and transposon insertion-site sequencing (Tn-Seq) to identify the full arsenal of P. mirabilis HI4320 fitness factors for single-species versus polymicrobial CAUTI with Providencia stuartii BE2467. 436 genes in the input pools lacked transposon insertions and were therefore concluded to be essential for P. mirabilis growth in rich medium. 629 genes were identified as P. mirabilis fitness factors during single-species CAUTI. Tn-Seq from coinfection with P. stuartii revealed 217/629 (35%) of the same genes as identified by single-species Tn-Seq, and 1353 additional factors that specifically contribute to colonization during coinfection. Mutants were constructed in eight genes of interest to validate the initial screen: 7/8 (88%) mutants exhibited the expected phenotypes for single-species CAUTI, and 3/3 (100%) validated the expected phenotypes for polymicrobial CAUTI. This approach provided validation of numerous previously described P. mirabilis fitness determinants from an ascending model of UTI, the discovery of novel fitness determinants specifically for CAUTI, and a stringent assessment of how polymicrobial infection influences fitness requirements. For instance, we describe a requirement for branched-chain amino acid biosynthesis by P. mirabilis during coinfection due to high-affinity import of leucine by P. stuartii. Further investigation of genes and pathways that provide a competitive advantage during both single-species and polymicrobial CAUTI will likely provide robust targets for therapeutic intervention to reduce P. mirabilis CAUTI incidence and severity.

Indexed as

AnimalsCatheter-Related InfectionsCoinfectionDisease Models, AnimalDNA Transposable ElementsGenetic FitnessHumansMiceMice, Inbred CBAMutagenesisProteus InfectionsProteus mirabilisUrinary Tract InfectionsVirulence FactorsDNA Transposable ElementsVirulence Factors

Identifiers

PMID28614382
PMCPMC5484520
OpenAlexW2625046072

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.