Evidence map›Paper›PMID 33378358›Full record

ArticlePLoS biology2020

Clustering of Tir during enteropathogenic E. coli infection triggers calcium influx-dependent pyroptosis in intestinal epithelial cells.

Qiyun Zhong, Theodoros I Roumeliotis, Zuza Kozik, Massiel Cepeda-Molero, Luis Ángel Fernández, Avinash R Shenoy, Chris Bakal, Gad Frankel, Jyoti S Choudhary

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

19 citing papers in PubMed, 28 citations in OpenAlex.

  1. EnteropathogeniceLife · 2026
    Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. The role of TRPV4 in programmed cell deaths.Molecular biology reports · 2024
    Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Yersiniabactin-ProducingInternational journal of molecular sciences · 2023
    Article
  15. Review
  16. Article
  17. Pyroptosis-Induced Inflammation and Tissue Damage.Journal of molecular biology · 2022
    Review
  18. Review
  19. 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

9 authors at 3 institutions in 2 countries.

Qiyun ZhongCentre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College, London, United Kingdom.ORCID 0000-0001-7053-9640
Theodoros I RoumeliotisFunctional Proteomics Group, Chester Beatty Laboratories, The Institute of Cancer Research, London, United Kingdom.ORCID 0000-0002-3354-5643
Zuza KozikFunctional Proteomics Group, Chester Beatty Laboratories, The Institute of Cancer Research, London, United Kingdom.
Massiel Cepeda-MoleroCentre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College, London, United Kingdom.
Luis Ángel FernándezDepartment of Microbial Biotechnology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Campus UAM-Cantoblanco, Madrid, Spain.
Avinash R ShenoyCentre for Molecular Bacteriology & Infection, Department of Infectious Disease, Imperial College, London, United Kingdom.
Chris BakalDynamical Cell Systems, Chester Beatty Laboratories, The Institute of Cancer Research, London, United Kingdom.ORCID 0000-0002-0413-6744
Gad FrankelCentre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College, London, United Kingdom.ORCID 0000-0002-0046-1363
Jyoti S ChoudharyFunctional Proteomics Group, Chester Beatty Laboratories, The Institute of Cancer Research, London, United Kingdom.ORCID 0000-0003-0881-5477
Imperial College London · GBInstitute of Cancer Research · GBConsejo Superior de Investigaciones Científicas · ES

Funding

Cancer Research UK 20146Cancer Research UK C309/A25144Medical Research Council MR/P028225/1Wellcome TrustWellcome Trust 107057/Z/15/Z
6 · The paper itself

Abstract

Clustering of the enteropathogenic Escherichia coli (EPEC) type III secretion system (T3SS) effector translocated intimin receptor (Tir) by intimin leads to actin polymerisation and pyroptotic cell death in macrophages. The effect of Tir clustering on the viability of EPEC-infected intestinal epithelial cells (IECs) is unknown. We show that EPEC induces pyroptosis in IECs in a Tir-dependent but actin polymerisation-independent manner, which was enhanced by priming with interferon gamma (IFNγ). Mechanistically, Tir clustering triggers rapid Ca2+ influx, which induces lipopolysaccharide (LPS) internalisation, followed by activation of caspase-4 and pyroptosis. Knockdown of caspase-4 or gasdermin D (GSDMD), translocation of NleF, which blocks caspase-4 or chelation of extracellular Ca2+, inhibited EPEC-induced cell death. IEC lines with low endogenous abundance of GSDMD were resistant to Tir-induced cell death. Conversely, ATP-induced extracellular Ca2+ influx enhanced cell death, which confirmed the key regulatory role of Ca2+ in EPEC-induced pyroptosis. We reveal a novel mechanism through which infection with an extracellular pathogen leads to pyroptosis in IECs.

Indexed as

ActinsAdhesins, BacterialCalciumCluster AnalysisEnteropathogenic Escherichia coliEpithelial CellsEscherichia coli InfectionsEscherichia coli ProteinsHeLa CellsHumansIntestinal MucosaIntestinesIntracellular Signaling Peptides and ProteinsPhosphate-Binding ProteinsProtein TransportPyroptosisActinsAdhesins, BacterialCalciumeaeA protein, E coliEscherichia coli ProteinsIntracellular Signaling Peptides and ProteinsPhosphate-Binding ProteinsReceptors, Cell SurfaceTir protein, E coliType III Secretion Systems

Identifiers

PMID33378358
PMCPMC7773185
OpenAlexW3116469082

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.