Evidence map›Paper›PMID 33355403›Full record

ArticleCellular microbiology2021

Very long O-antigen chains of Salmonella Paratyphi A inhibit inflammasome activation and pyroptotic cell death.

Elli Mylona, Julia Sanchez-Garrido, Trang Nguyen Hoang Thu, Sabina Dongol, Abhilasha Karkey, Stephen Baker, Avinash R Shenoy, Gad Frankel

Open access · hybridAbstract read
In one paragraph

Article in Cellular microbiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

21 citing papers in PubMed, 25 citations in OpenAlex.

  1. [Pathophysiologically complex bilateral profound sensorineural hearing loss in the setting of type 2 diabetes mellitus and fungal sepsis: a case report].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2026
    Article
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  3. A defined microbiota mouse model forFrontiers in microbiology · 2026
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  4. Protein-centric mechanisms of typhoidalFrontiers in cellular and infection microbiology · 2026
    Review
  5. Comparative genomics ofVirulence · 2025
    Article
  6. Review
  7. Article
  8. Journal of inflammation research · 2025
    Review
  9. Mutation inVeterinary sciences · 2024
    Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Pyroptosis regulation byFrontiers in immunology · 2024
    Review
  15. Pyroptosis in microbial infectious diseases.Molecular biology reports · 2023
    Review
  16. Article
  17. Review
  18. Article
  19. 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

8 authors at 4 institutions in 4 countries.

Elli MylonaDepartment of Life Sciences, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK.ORCID 0000-0002-2638-0713
Julia Sanchez-GarridoDepartment of Life Sciences, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK.
Trang Nguyen Hoang ThuOxford University Clinical Research Unit, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Sabina DongolOxford University Clinical Research Unit, Patan Academy of Health Sciences, Kathmandu, Nepal.
Abhilasha KarkeyOxford University Clinical Research Unit, Patan Academy of Health Sciences, Kathmandu, Nepal.
Stephen BakerCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, UK.
Avinash R ShenoyDepartment of Infectious Disease, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK.ORCID 0000-0001-6228-9303
Gad FrankelDepartment of Life Sciences, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK.ORCID 0000-0002-0046-1363
Imperial College London · GBPatan Academy of Health Sciences · NPUniversity of Cambridge · GBOxford University Clinical Research Unit · VN

Funding

Medical Research Council MR/P022138/1Medical Research Council MR/P028225/1Wellcome TrustWellcome Trust 107057/Z/15/Z
6 · The paper itself

Abstract

Salmonella Paratyphi A (SPtA) remains one of the leading causes of enteric (typhoid) fever. Yet, despite the recent increased rate of isolation from patients in Asia, our understanding of its pathogenesis is incomplete. Here we investigated inflammasome activation in human macrophages infected with SPtA. We found that SPtA induces GSDMD-mediated pyroptosis via activation of caspase-1, caspase-4 and caspase-8. Although we observed no cell death in the absence of a functional Salmonella pathogenicity island-1 (SPI-1) injectisome, HilA-mediated overexpression of the SPI-1 regulon enhances pyroptosis. SPtA expresses FepE, an LPS O-antigen length regulator, which induces the production of very long O-antigen chains. Using a ΔfepE mutant we established that the very long O-antigen chains interfere with bacterial interactions with epithelial cells and impair inflammasome-mediated macrophage cell death. Salmonella Typhimurium (STm) serovar has a lower FepE expression than SPtA, and triggers higher pyroptosis, conversely, increasing FepE expression in STm reduced pyroptosis. These results suggest that differential expression of FepE results in serovar-specific inflammasome modulation, which mirrors the pro- and anti-inflammatory strategies employed by STm and SPtA, respectively. Our studies point towards distinct mechanisms of virulence of SPtA, whereby it attenuates inflammasome-mediated detection through the elaboration of very long LPS O-polysaccharides.

Indexed as

PyroptosisBacterial ProteinsCaspasesGasderminsHeLa CellsHumansInflammasomesIntracellular Signaling Peptides and ProteinsMacrophagesO AntigensParatyphoid FeverPhosphate-Binding ProteinsSalmonella paratyphi ATHP-1 CellsType III Secretion SystemsVirulenceBacterial ProteinsCaspasesGasderminsGSDMD protein, humanInflammasomesIntracellular Signaling Peptides and ProteinsO AntigensPhosphate-Binding ProteinsSpi1 protein, SalmonellaType III Secretion SystemsVirulence Factorscaspase-4enteric feverFepEinflammasomesO-antigenpyroptosisSalmonella Paratyphi ASalmonella Typhimurium

Identifiers

PMID33355403
PMCPMC8609438
OpenAlexW3117629661

What OpenQuestion holds

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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.