Evidence map›Paper›PMID 23716613›Full record

ArticleInfection and immunity2013

Phosphatidylinositol 4,5-bisphosphate is a novel coactivator of the Pseudomonas aeruginosa cytotoxin ExoU.

Gregory H Tyson, Alan R Hauser

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

31 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
  2. Molecular Mechanisms Underlying the Pathogenicity ofMedicina (Kaunas, Lithuania) · 2026
    Review
  3. Review
  4. Catheter-associated urinary tract infection byProceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  5. ThemBio · 2022
    Article
  6. Article
  7. Article
  8. Perspectives on theToxins · 2021
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Tetradecanoic Acids With Anti-Virulence Properties Increase the Pathogenicity ofFrontiers in cellular and infection microbiology · 2020
    Article
  15. Microorganisms · 2019
    Review
  16. Interactions of the effector ExoU fromThe Journal of biological chemistry · 2019
    Article
  17. Review
  18. Article
  19. Article
  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

2 authors at 1 institution in 1 country.

Gregory H TysonDepartment of Microbiology/Immunology, Northwestern University, Chicago, Illinois, USA.
Alan R Hauser
Northwestern University · US

Funding

Mechanistic Studies of Patatin-like ToxinsR01AI053674 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI HAUSER, ALAN R · 2003 to 2017
$4.3M
Validating targets in p. aeruginosa type III secretion using chemical probesR01AI099269 · NIAID · MICROBIOTIX, INC · PI MOIR, DONALD T · 2012 to 2015
$3.2M
Pseudomonas aeruginosa Genomic Islands and VirulenceR01AI075191 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI HAUSER, ALAN R · 2009 to 2013
$1.7M
Patient-Oriented Research on Pseudomonas aeruginosaK24AI104831 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI HAUSER, ALAN R · 2013 to 2024
$1.2M
Mechanism of Azithromycin Activity in Pseudomonas InfectionsR21AI088286 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI HAUSER, ALAN R · 2010 to 2011
$438k
NIAID NIH HHS AI053674NIAID NIH HHS AI075191NIAID NIH HHS AI088286NIAID NIH HHS AI099269NIAID NIH HHS K24 AI104831NIAID NIH HHS R01 AI053674NIAID NIH HHS R01 AI075191NIAID NIH HHS R01 AI099269NIAID NIH HHS R21 AI088286
6 · The paper itself

Abstract

ExoU is a potent phospholipase A2 effector protein secreted by the type III secretion system of Pseudomonas aeruginosa. By cleaving plasma membrane phospholipids, it causes rapid lysis of eukaryotic cells. However, ExoU does not exhibit activity on its own but instead requires eukaryotic cell cofactors for activation. Ubiquitin and ubiquitinated proteins have been shown to activate ExoU, but previous work suggested that other cofactors are also involved. In this study, we demonstrate that phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is another important coactivator of ExoU. PI(4,5)P2 works synergistically with ubiquitin to greatly enhance the phospholipase A2 activity of ExoU. Distinct residues of ExoU were critical for activation by PI(4,5)P2 and by ubiquitin, indicating that these factors activate ExoU by discrete mechanisms. In support of the biological relevance of PI(4,5)P2 coactivation, a yeast mutant with reduced PI(4,5)P2 levels was less susceptible to the cytotoxic activity of ExoU. Together, these findings further elaborate the molecular mechanism of ExoU.

Indexed as

Bacterial ProteinsCoenzymesEnzyme ActivationImmunoblottingPhosphatidylinositol 4,5-DiphosphatePseudomonas aeruginosaPseudomonas InfectionsBacterial ProteinsCoenzymesPhosphatidylinositol 4,5-Diphosphatepseudomonas exoprotein A protein, Pseudomonas aeruginosa

Identifiers

PMID23716613
PMCPMC3719568
OpenAlexW2099284920

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.