Evidence map›Paper›PMID 26252386›Full record

ArticlePloS one2015

Homogentisate 1-2-Dioxygenase Downregulation in the Chronic Persistence of Pseudomonas aeruginosa Australian Epidemic Strain-1 in the CF Lung.

Christopher J Harmer, Matthew Wynn, Rachel Pinto, Stuart Cordwell, Barbara R Rose, Colin Harbour, James A Triccas, Jim Manos

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Christopher J HarmerBacterial Pathogens in Cystic Fibrosis Group, Department of Infectious Diseases and Immunology, Central Clinical School, The University of Sydney, Sydney, Australia; School of Molecular Biosciences, The University of Sydney, Sydney, Australia.
Matthew WynnBacterial Pathogens in Cystic Fibrosis Group, Department of Infectious Diseases and Immunology, Central Clinical School, The University of Sydney, Sydney, Australia.
Rachel PintoMicrobial Pathogenesis and Immunity Group, Department of Infectious Diseases and Immunology, Central Clinical School, The University of Sydney, Sydney, Australia.
Stuart CordwellSchool of Molecular Biosciences, The University of Sydney, Sydney, Australia.
Barbara R RoseBacterial Pathogens in Cystic Fibrosis Group, Department of Infectious Diseases and Immunology, Central Clinical School, The University of Sydney, Sydney, Australia.
Colin HarbourBacterial Pathogens in Cystic Fibrosis Group, Department of Infectious Diseases and Immunology, Central Clinical School, The University of Sydney, Sydney, Australia.
James A TriccasMicrobial Pathogenesis and Immunity Group, Department of Infectious Diseases and Immunology, Central Clinical School, The University of Sydney, Sydney, Australia.
Jim ManosBacterial Pathogens in Cystic Fibrosis Group, Department of Infectious Diseases and Immunology, Central Clinical School, The University of Sydney, Sydney, Australia.
University of Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Some Pseudomonas aeruginosa strains including Australian Epidemic Strain-1 (AES-1 or AUS-01) cause persistent chronic infection in cystic fibrosis (CF) patients, with greater morbidity and mortality. Factors conferring persistence are largely unknown. Previously we analysed the transcriptomes of AES-1 grown in Luria broth, nematode growth medium for Caenorhabditis elegans assay (both aerobic) and artificial sputum medium (mainly hypoxic). Transcriptional comparisons included chronic AES-1 strains against PAO1 and acute AES-1 (AES-1R) against its chronic isogen (AES-1M), isolated 10.5 years apart from a CF patient and not eradicated in the meantime. Prominent amongst genes downregulated in AES-1M in all comparisons was homogentisate-1-2-dioxygenase (hmgA); an oxygen-dependent gene known to be mutationally deactivated in many chronic infection strains of P. aeruginosa. To investigate if hmgA downregulation and deactivation gave similar virulence persistence profiles, a hmgA mutant made in UCBPP-PA14 utilising RedS-recombinase and AES-1M were assessed in the C. elegans virulence assay, and the C57BL/6 mouse for pulmonary colonisation and TNF-α response. In C. elegans, hmgA deactivation resulted in significantly increased PA14 virulence while hmgA downregulation reduced AES-1M virulence. AES-1M was significantly more persistent in mouse lung and showed a significant increase in TNF-α (p<0.0001), sustained even with no detectable bacteria. PA14ΔhmgA did not show increased TNF-α. This study suggests that hmgA may have a role in P. aeruginosa persistence in chronic infection and the results provide a starting point for clarifying the role of hmgA in chronic AES-1.

Indexed as

Down-RegulationAnimalsAustraliaBacterial ProteinsCaenorhabditis elegansCystic FibrosisDisease Models, AnimalEpidemicsFemaleFlow CytometryGenotypeHomogentisate 1,2-DioxygenaseImmunophenotypingLungMice, Inbred C57BLMutationBacterial ProteinsHomogentisate 1,2-DioxygenaseTumor Necrosis Factor-alpha

Identifiers

PMID26252386
PMCPMC4529145
OpenAlexW1111185855

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.