Evidence map›Paper›PMID 25422265›Full record

ArticleInfection and immunity2015

Coxiella burnetii effector proteins that localize to the parasitophorous vacuole membrane promote intracellular replication.

Charles L Larson, Paul A Beare, Daniel E Voth, Dale Howe, Diane C Cockrell, Robert J Bastidas, Raphael H Valdivia, Robert A Heinzen

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
6.8field-weighted citation impact, top 2% 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

67 citing papers in PubMed, 92 citations in OpenAlex.

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  17. Archives of Razi Institute · 2023
    Review
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  20. Identification of essential genes inMicrobial genomics · 2023
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7 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

8 authors at 4 institutions in 1 country.

Charles L LarsonCoxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
Paul A BeareCoxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
Daniel E VothDepartment of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Dale HoweCoxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
Diane C CockrellCoxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
Robert J BastidasDepartment of Molecular Genetics and Microbiology, Center for Microbial Pathogenesis, Duke University, Durham, North Carolina, USA.
Raphael H ValdiviaDepartment of Molecular Genetics and Microbiology, Center for Microbial Pathogenesis, Duke University, Durham, North Carolina, USA.
Robert A HeinzenCoxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA rheinzen@niaid.nih.gov.
National Institutes of Health · USDuke University · USNational Institute of Allergy and Infectious Diseases · USUniversity of Arkansas for Medical Sciences · US

Funding

Cellular and Developmental Biology of Coxiella burnetiiZIAAI000931 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI HEINZEN, ROBERT A · 2009 to 2023
$11.8M
Role of the Coxiella burnetii Cryptic Plasmid in Host Cell ParasitismR01AI087669 · NIAID · UNIV OF ARKANSAS FOR MED SCIS · PI VOTH, DANIEL E · 2010 to 2014
$1.9M
Identification of Coxiella burnetti Effector ProteinsR21AI072485 · NIAID · DUKE UNIVERSITY · PI VALDIVIA, RAPHAEL H · 2007 to 2008
$425k
Intramural NIH HHSNIAID NIH HHS AI072485NIAID NIH HHS R01 AI087669NIAID NIH HHS R01AI087669NIAID NIH HHS R21 AI072485
6 · The paper itself

Abstract

The intracellular bacterial pathogen Coxiella burnetii directs biogenesis of a parasitophorous vacuole (PV) that acquires host endolysosomal components. Formation of a PV that supports C. burnetii replication requires a Dot/Icm type 4B secretion system (T4BSS) that delivers bacterial effector proteins into the host cell cytosol. Thus, a subset of T4BSS effectors are presumed to direct PV biogenesis. Recently, the PV-localized effector protein CvpA was found to promote C. burnetii intracellular growth and PV expansion. We predict additional C. burnetii effectors localize to the PV membrane and regulate eukaryotic vesicle trafficking events that promote pathogen growth. To identify these vacuolar effector proteins, a list of predicted C. burnetii T4BSS substrates was compiled using bioinformatic criteria, such as the presence of eukaryote-like coiled-coil domains. Adenylate cyclase translocation assays revealed 13 proteins were secreted in a Dot/Icm-dependent fashion by C. burnetii during infection of human THP-1 macrophages. Four of the Dot/Icm substrates, termed Coxiella vacuolar protein B (CvpB), CvpC, CvpD, and CvpE, labeled the PV membrane and LAMP1-positive vesicles when ectopically expressed as fluorescently tagged fusion proteins. C. burnetii ΔcvpB, ΔcvpC, ΔcvpD, and ΔcvpE mutants exhibited significant defects in intracellular replication and PV formation. Genetic complementation of the ΔcvpD and ΔcvpE mutants rescued intracellular growth and PV generation, whereas the growth of C. burnetii ΔcvpB and ΔcvpC was rescued upon cohabitation with wild-type bacteria in a common PV. Collectively, these data indicate C. burnetii encodes multiple effector proteins that target the PV membrane and benefit pathogen replication in human macrophages.

Indexed as

Bacterial ProteinsBacterial Secretion SystemsCell Line, TumorCell MembraneCoxiella burnetiiCytosolGene DeletionHeLa CellsHost-Pathogen InteractionsHumansMacrophagesProtein TransportQ FeverRecombinant Fusion ProteinsVacuolesBacterial ProteinsBacterial Secretion SystemsRecombinant Fusion Proteins

Identifiers

PMID25422265
PMCPMC4294226
OpenAlexW2120461496

What OpenQuestion holds

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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.