Evidence map›Paper›PMID 22337879›Full record

ArticleThe Journal of biological chemistry2012

Distinct roles of secreted HtrA proteases from gram-negative pathogens in cleaving the junctional protein and tumor suppressor E-cadherin.

Benjamin Hoy, Tim Geppert, Manja Boehm, Felix Reisen, Patrick Plattner, Gabriele Gadermaier, Norbert Sewald, Fatima Ferreira, Peter Briza, Gisbert Schneider and 2 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.

0numbers the graph read from it
0cells of the map it votes in
108citing papers in PubMed
11.8field-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

108 citing papers in PubMed, 165 citations in OpenAlex.

  1. Host andGut microbes · 2026
    Article
  2. Review
  3. Review
  4. Serine protease HtrA promotesScience advances · 2026
    Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. The immunopathogenesis ofFrontiers in microbiology · 2024
    Review
  16. Host-Cell-Dependent Roles of E-Cadherin inInternational journal of molecular sciences · 2023
    Article
  17. Identification and Characterization of an HtrA Sheddase Produced byInternational journal of molecular sciences · 2023
    Article
  18. Article
  19. Review
  20. Molecular Targets inBiomolecules · 2023
    Review

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

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

12 authors at 4 institutions in 4 countries.

Benjamin HoyDivision of Microbiology, University Salzburg, 5020 Salzburg, Austria.
Tim GeppertDepartment of Chemistry and Applied Biosciences, ETH Zürich, 8092 Zurich, Switzerland.
Manja BoehmSchool of Biomolecular and Biomedical Sciences, University College Dublin, Dublin 4, Ireland, and.
Felix ReisenDepartment of Chemistry and Applied Biosciences, ETH Zürich, 8092 Zurich, Switzerland.
Patrick PlattnerDepartment of Chemistry, Organic and Bioorganic Chemistry, Bielefeld University, D-33501 Bielefeld, Germany.
Gabriele GadermaierChristian Doppler Laboratory for Allergy Diagnosis and Therapy, University Salzburg, 5020 Salzburg, Austria.
Norbert SewaldDepartment of Chemistry, Organic and Bioorganic Chemistry, Bielefeld University, D-33501 Bielefeld, Germany.
Fatima FerreiraChristian Doppler Laboratory for Allergy Diagnosis and Therapy, University Salzburg, 5020 Salzburg, Austria.
Peter BrizaChristian Doppler Laboratory for Allergy Diagnosis and Therapy, University Salzburg, 5020 Salzburg, Austria.
Gisbert SchneiderDepartment of Chemistry and Applied Biosciences, ETH Zürich, 8092 Zurich, Switzerland.
Steffen BackertSchool of Biomolecular and Biomedical Sciences, University College Dublin, Dublin 4, Ireland, and.
Silja WesslerDivision of Microbiology, University Salzburg, 5020 Salzburg, Austria. Electronic address: silja.wessler@sbg.ac.at.
ETH Zurich · CHBielefeld University · DEUniversity College Dublin · IEUniversity of Salzburg · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The periplasmic chaperone and serine protease HtrA is important for bacterial stress responses and protein quality control. Recently, we discovered that HtrA from Helicobacter pylori is secreted and cleaves E-cadherin to disrupt the epithelial barrier, but it remained unknown whether this maybe a general virulence mechanism. Here, we show that important other pathogens including enteropathogenic Escherichia coli, Shigella flexneri, and Campylobacter jejuni, but not Neisseria gonorrhoeae, cleaved E-cadherin on host cells. HtrA deletion in C. jejuni led to severe defects in E-cadherin cleavage, loss of cell adherence, paracellular transmigration, and basolateral invasion. Computational modeling of HtrAs revealed a conserved pocket in the active center exhibiting pronounced proteolytic activity. Differential E-cadherin cleavage was determined by an alanine-to-glutamine exchange in the active center of neisserial HtrA. These data suggest that HtrA-mediated E-cadherin cleavage is a prevalent pathogenic mechanism of multiple gram-negative bacteria representing an attractive novel target for therapeutic intervention to combat bacterial infections.

Indexed as

ProteolysisBacterial ProteinsCaco-2 CellsCadherinsGram-Negative BacteriaGram-Negative Bacterial InfectionsHumansSerine EndopeptidasesTumor Suppressor ProteinsBacterial ProteinsCadherinsSerine EndopeptidasesTumor Suppressor Proteins

Identifiers

PMID22337879
PMCPMC3323053
OpenAlexW2035688360

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.