Evidence map›Paper›PMID 26417105›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Ubiquitin systems mark pathogen-containing vacuoles as targets for host defense by guanylate binding proteins.

Arun K Haldar, Clémence Foltz, Ryan Finethy, Anthony S Piro, Eric M Feeley, Danielle M Pilla-Moffett, Masaki Komatsu, Eva-Maria Frickel, Jörn Coers

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed
14.7field-weighted citation impact, top 1% 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

112 citing papers in PubMed, 171 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. TheeLife · 2025
    Article
  5. Review
  6. Article
  7. Phosphatidic acid production on the vacuole harboringProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  8. ThebioRxiv : the preprint server for biology · 2025
    Article
  9. Cell-Autonomous Immunity: From Cytosolic Sensing to Self-Defense.International journal of molecular sciences · 2025
    Review
  10. Article
  11. Autophagy and Bacterial infections.Autophagy reports · 2025
    Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Structural basis of Irgb6 inactivation by Toxoplasma gondii through the phosphorylation of switch I.Genes to cells : devoted to molecular & cellular mechanisms · 2024
    Article
  17. Review
  18. Review
  19. Article
  20. Human GBP1 Is Involved in the Repair of Damaged Phagosomes/Endolysosomes.International journal of molecular sciences · 2023
    Article

52 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

9 authors at 5 institutions in 3 countries.

Arun K HaldarDepartments of Molecular Genetics and Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710;
Clémence FoltzThe Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, United Kingdom;
Ryan FinethyDepartments of Molecular Genetics and Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710;
Anthony S PiroDepartments of Molecular Genetics and Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710;
Eric M FeeleyDepartments of Molecular Genetics and Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710;
Danielle M Pilla-MoffettDepartments of Molecular Genetics and Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710;
Masaki KomatsuDepartment of Biochemistry, School of Medicine Niigata University, Niigata-shi, 951-8510, Japan.
Eva-Maria FrickelThe Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, United Kingdom;
Jörn CoersDepartments of Molecular Genetics and Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710; jorn.coers@duke.edu.
Duke Medical Center · USDuke University · USDuke University Hospital · USThe Francis Crick Institute · GBNiigata University · JP

Funding

ORGANIZATION AND FUNCTIONS OF CELLULAR STRUCTUREST32GM007184 · NIGMS · DUKE UNIVERSITY · PI JINKS-ROBERTSON, SUE · 1985 to 2019
$18.2M
IRGM-driven host responses to Chlamydia trachomatis infectionsR01AI103197 · NIAID · DUKE UNIVERSITY · PI COERS, JOERN · 2013 to 2023
$4.2M
Interferon-inducible cell-intrinsic host defense against Chlamydia trachomatisR37AI103197 · NIAID · DUKE UNIVERSITY · PI Jorn Coers · 2024 to 2026
$1.6M
Medical Research Council MC_UP_1202/12NIAID NIH HHS R01 AI103197NIAID NIH HHS R01AI103197NIAID NIH HHS R37 AI103197NIGMS NIH HHS T32 GM007184Wellcome Trust
6 · The paper itself

Abstract

Many microbes create and maintain pathogen-containing vacuoles (PVs) as an intracellular niche permissive for microbial growth and survival. The destruction of PVs by IFNγ-inducible guanylate binding protein (GBP) and immunity-related GTPase (IRG) host proteins is central to a successful immune response directed against numerous PV-resident pathogens. However, the mechanism by which IRGs and GBPs cooperatively detect and destroy PVs is unclear. We find that host cell priming with IFNγ prompts IRG-dependent association of Toxoplasma- and Chlamydia-containing vacuoles with ubiquitin through regulated translocation of the E3 ubiquitin ligase tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6). This initial ubiquitin labeling elicits p62-mediated escort and deposition of GBPs to PVs, thereby conferring cell-autonomous immunity. Hypervirulent strains of Toxoplasma gondii evade this process via specific rhoptry protein kinases that inhibit IRG function, resulting in blockage of downstream PV ubiquitination and GBP delivery. Our results define a ubiquitin-centered mechanism by which host cells deliver GBPs to PVs and explain how hypervirulent parasites evade GBP-mediated immunity.

Indexed as

Immune EvasionAnimalsChlamydia InfectionsChlamydia trachomatisGTP-Binding ProteinsImmunity, InnateMiceMice, KnockoutTNF Receptor-Associated Factor 6ToxoplasmaToxoplasmosisUbiquitinUbiquitin-Protein LigasesVacuolesGTP-Binding ProteinsTNF Receptor-Associated Factor 6UbiquitinUbiquitin-Protein LigasesChlamydiaGBPsimmunity-related GTPaseinterferonToxoplasma

Identifiers

PMID26417105
PMCPMC4611635
OpenAlexW2173334724

What OpenQuestion holds

Textmetadata
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.