Evidence map›Paper›PMID 30232373›Full record

ArticleScientific reports2018

Pseudomonas aeruginosa ExoS Induces Intrinsic Apoptosis in Target Host Cells in a Manner That is Dependent on its GAP Domain Activity.

Amber Kaminski, Kajal H Gupta, Josef W Goldufsky, Ha Won Lee, Vineet Gupta, Sasha H Shafikhani

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

35 citing papers in PubMed, 46 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Molecular Mechanisms Underlying the Pathogenicity ofMedicina (Kaunas, Lithuania) · 2026
    Review
  5. The longitudinal expression ofMicrobiology (Reading, England) · 2026
    Article
  6. Virulence · 2025
    Article
  7. Advances inMicroorganisms · 2025
    Review
  8. Review
  9. Mapping genetic and phenotypic diversity ofbioRxiv : the preprint server for biology · 2025
    Article
  10. Article
  11. Article
  12. Exploring interspecies differences inJournal of medical microbiology · 2024
    Article
  13. Article
  14. Review
  15. International journal of microbiology · 2024
    Article
  16. Article
  17. Review
  18. The RIPK3 Scaffold Regulates Lung Inflammation DuringAmerican journal of respiratory cell and molecular biology · 2023
    Article
  19. Cells · 2023
    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 1 institution in 1 country.

Amber KaminskiDepartment of Medicine, Rush University Medical Center, Chicago, IL, USA.ORCID 0000-0003-4181-2972
Kajal H GuptaDepartment of Medicine, Rush University Medical Center, Chicago, IL, USA.
Josef W GoldufskyDepartment of Medicine, Rush University Medical Center, Chicago, IL, USA.
Ha Won LeeDepartment of Medicine, Rush University Medical Center, Chicago, IL, USA.
Vineet GuptaDepartment of Medicine, Rush University Medical Center, Chicago, IL, USA.ORCID 0000-0001-6987-2550
Sasha H ShafikhaniDepartment of Medicine, Rush University Medical Center, Chicago, IL, USA. Sasha_Shafikhani@rush.edu.ORCID 0000-0003-1755-9997
Rush University Medical Center · US

Funding

Factors Leading to Enhanced Pseudomonas Aeruginosa Infection in Diabetic WoundsR01DK107713 · NIDDK · RUSH UNIVERSITY MEDICAL CENTER · PI SHAFIKHANI, SASHA H · 2016 to 2020
$1.7M
U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) RO1DK107713
6 · The paper itself

Abstract

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes serious infections in immunocompromised individuals and cystic fibrosis patients. ExoS and ExoT are two homologous bifunctional Type III Secretion System (T3SS) virulence factors that induce apoptosis in target host cells. They possess a GTPase Activating Protein (GAP) domain at their N-termini, which share ~76% homology, and an ADP-ribosyltransferase (ADPRT) domain at their C-termini, which target non-overlapping substrates. Both the GAP and the ADPRT domains contribute to ExoT's cytotoxicity in target epithelial cells, whereas, ExoS-induced apoptosis is reported to be primarily due to its ADPRT domain. In this report, we demonstrate that ExoS/GAP domain is both necessary and sufficient to induce mitochondrial apoptosis. Our data demonstrate that intoxication with ExoS/GAP domain leads to enrichment of Bax and Bim into the mitochondrial outer-membrane, disruption of mitochondrial membrane and release of and cytochrome c into the cytosol, which activates initiator caspase-9 and effector caspase-3, that executes cellular death. We posit that the contribution of the GAP domain in ExoS-induced apoptosis was overlooked in prior studies due to its slower kinetics of cytotoxicity as compared to ADPRT. Our data clarify the field and reveal a novel virulence function for ExoS/GAP as an inducer of apoptosis.

Indexed as

ADP Ribose TransferasesApoptosisBacterial ToxinsBcl-2-Like Protein 11Caspase 3Caspase 9Cell Cycle ProteinsChondroitin Sulfate ProteoglycansChromosomal Proteins, Non-HistoneCytochromes cCytosolHeLa CellsHumansMitochondriaProtein DomainsPseudomonas aeruginosaADP Ribose TransferasesBacterial ToxinsBCL2L11 protein, humanBcl-2-Like Protein 11CASP3 protein, humanCASP9 protein, humanCaspase 3Caspase 9Cell Cycle ProteinsChondroitin Sulfate ProteoglycansChromosomal Proteins, Non-HistoneCytochromes cexoenzyme SSMC3 protein, human

Identifiers

PMID30232373
PMCPMC6145893
OpenAlexW2889696052

What OpenQuestion holds

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Registered trials

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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.