Evidence map›Paper›PMID 24119232›Full record

ArticleCellular microbiology2014

Burkholderia cenocepacia J2315 escapes to the cytosol and actively subverts autophagy in human macrophages.

Souhaila Al-Khodor, Kimberly Marshall-Batty, Vinod Nair, Li Ding, David E Greenberg, Iain D C Fraser

Open access · bronzeAbstract read
In one paragraph

Article in Cellular microbiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.2field-weighted citation impact, top 9% 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

28 citing papers in PubMed, 37 citations in OpenAlex.

  1. A type VI secretion system inInfection and immunity · 2024
    Article
  2. Review
  3. Emerging Concepts in Defective Macrophage Phagocytosis in Cystic Fibrosis.International journal of molecular sciences · 2022
    Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Bacterial Subversion of Autophagy in Cystic Fibrosis.Frontiers in cellular and infection microbiology · 2021
    Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. NADPH Oxidase Deficiency: A Multisystem Approach.Oxidative medicine and cellular longevity · 2017
    Review
  19. Review
  20. Article
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

6 authors at 3 institutions in 1 country.

Souhaila Al-KhodorSignaling Systems Unit, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Kimberly Marshall-Batty
Vinod Nair
Li Ding
David E Greenberg
Iain D C Fraser
National Institutes of Health · USThe University of Texas Southwestern Medical Center · USNational Institute of Allergy and Infectious Diseases · US

Funding

Infectious Diseases Research Technologies Core - RMLZICAI001052 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CHERRY, JAMES · 2009 to 2025
$133.3M
RNAi Screening in Hematopoietic CellsZIAAI001106 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI FRASER, IAIN · 2009 to 2025
$12.4M
Analysis of Innate Immune Signaling NetworksZIAAI001107 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI FRASER, IAIN · 2009 to 2025
$11.9M
Intramural NIH HHS ZIA AI001106Intramural NIH HHS ZIA AI001107
6 · The paper itself

Abstract

Selective autophagy functions to specifically degrade cellular cargo tagged by ubiquitination, including bacteria. Strains of the Burkholderia cepacia complex (Bcc) are opportunistic pathogens that cause life-threatening infections in patients with cystic fibrosis (CF) and chronic granulomatous disease (CGD). While there is evidence that defective macrophage autophagy in a mouse model of CF can influence B. cenocepacia susceptibility, there have been no comprehensive studies on how this bacterium is sensed and targeted by the host autophagy response in human macrophages. Here, we describe the intracellular life cycle of B. cenocepacia J2315 and its interaction with the autophagy pathway in human cells. Electron and confocal microscopy analyses demonstrate that the invading bacteria interact transiently with the endocytic pathway before escaping to the cytosol. This escape triggers theselective autophagy pathway, and the recruitment of ubiquitin, the ubiquitin-binding adaptors p62 and NDP52 and the autophagosome membrane-associated protein LC3B, to the bacterial vicinity. However, despite recruitment of these key autophagy pathway effectors, B. cenocepacia blocks autophagosome completion and replicates in the host cytosol. We find that a pre-infection increase in cellular autophagy flux can significantly inhibit B. cenocepacia replication and that lower autophagy flux in macrophages from immunocompromised CGD patients could contribute to increased B. cenocepacia susceptibility, identifying autophagy manipulation as a potential therapeutic approach to reduce bacterial burden in B. cenocepacia infections.

Indexed as

Immune EvasionAdaptor Proteins, Signal TransducingAnimalsAutophagyBurkholderia cenocepaciaBurkholderia InfectionsCell LineCytosolDisease Models, AnimalEndoplasmic ReticulumHumansMacrophagesMiceMice, Inbred C57BLMicrotubule-Associated ProteinsNuclear ProteinsAdaptor Proteins, Signal TransducingCALCOCO2 protein, humanMAP1LC3B protein, humanMicrotubule-Associated ProteinsNuclear ProteinsRNA, Small InterferingSequestosome-1 ProteinSQSTM1 protein, human

Identifiers

PMID24119232
PMCPMC3927784
OpenAlexW1597012755

What OpenQuestion holds

Textmetadata
LicenceTDM
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.