Evidence map›Paper›PMID 22308473›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2012

The protein SdhA maintains the integrity of the Legionella-containing vacuole.

Elizabeth A Creasey, Ralph R Isberg

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.

0numbers the graph read from it
0cells of the map it votes in
118citing papers in PubMed
12.6field-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

118 citing papers in PubMed, 199 citations in OpenAlex.

  1. Trial
  2. RNF213-dependent lytic destruction ofProceedings of the National Academy of Sciences of the United States of America · 2026
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  7. Phosphatidic acid production on the vacuole harboringProceedings of the National Academy of Sciences of the United States of America · 2025
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  12. Pattern Recognition by NOD-Like Receptors.Advances in experimental medicine and biology · 2025
    Review
  13. Review
  14. Journal of bacteriology · 2024
    Review
  15. Article
  16. Article
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  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Elizabeth A CreaseyDepartment of Molecular Biology and , Tufts University School of Medicine, Boston, MA 02111, USA
Ralph R Isberg
Tufts University · US

Funding

Howard Hughes Medical Institute
6 · The paper itself

Abstract

Legionella pneumophila directs the formation of a specialized vacuole within host cells, dependent on protein substrates of the Icm/Dot translocation system. Survival of the host cell is essential for intracellular replication of L. pneumophila. Strains lacking the translocated substrate SdhA are defective for intracellular replication and activate host cell death pathways in primary macrophages. To understand how SdhA promotes evasion of death pathways, we performed a mutant hunt to identify bacterial suppressors of the ΔsdhA growth defect. We identified the secreted phospholipase PlaA as key to activation of death pathways by the ΔsdhA strain. Based on homology between PlaA and SseJ, a Salmonella protein associated with vacuole degradation, we determined the roles of SdhA and PlaA in controlling vacuole integrity. In the absence of sdhA, the Legionella-containing vacuole was unstable, resulting in access to the host cytosol. Both vacuole disruption and host cell death were largely dependent on PlaA. Consistent with these observations, the ΔsdhA strain colocalized with galectin-3, a marker of vacuole rupture, in a PlaA-dependent process. Access of ΔsdhA strains to the macrophage cytosol triggered multiple responses in the host cell, including degradation of bacteria, induction of the type I IFN response, and activation of inflammasomes. Therefore, we have demonstrated that the Legionella-containing vacuole is actively stabilized by the SdhA protein during intracellular replication. This vacuolar niche affords the bacterium protection from cytosolic host factors that degrade bacteria and initiate immune responses.

Indexed as

Amino Acid SequenceAnimalsBacterial ProteinsBiomarkersCell DeathCytosolFlagellinFlavoproteinsGalectin 3Gene DeletionHost-Pathogen InteractionsHumansLegionella pneumophilaMacrophagesMiceMice, Inbred ABacterial ProteinsBiomarkersflaA protein, bacteriaFlagellinFlavoproteinsGalectin 3PhospholipasesSdhA protein, Bacteria

Identifiers

PMID22308473
PMCPMC3295292
OpenAlexW2076490464

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.