Evidence map›Paper›PMID 19324080›Full record

ArticleMicrobial pathogenesis2009

Essential role of the glucosyltransferase activity in Clostridium difficile toxin-induced secretion of TNF-alpha by macrophages.

Xingmin Sun, Xiangyun He, Saul Tzipori, Ralf Gerhard, Hanping Feng

Open access · greenAbstract read
In one paragraph

Article in Microbial pathogenesis, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

33 citing papers in PubMed, 56 citations in OpenAlex.

  1. Review
  2. Mechanisms ofFrontiers in cellular and infection microbiology · 2025
    Review
  3. Article
  4. Review
  5. Article
  6. Large Clostridial Toxins: Mechanisms and Roles in Disease.Microbiology and molecular biology reviews : MMBR · 2021
    Review
  7. Article
  8. Enterotoxic Clostridia:Microbiology spectrum · 2019
    Review
  9. Review
  10. Article
  11. Article
  12. On and Off: A Dual Role for Cysteine Protease Autoprocessing ofCellular and molecular gastroenterology and hepatology · 2018
    Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Review
  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

5 authors at 2 institutions in 2 countries.

Xingmin SunDivision of Infectious Diseases, Department of Biomedical Sciences, Tufts University, Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
Xiangyun He
Saul Tzipori
Ralf Gerhard
Hanping Feng
Tufts University · USMedizinische Hochschule Hannover · DE

Funding

The role of dendritic cells in T cell immunity to CryptosporidiumK01DK076549 · NIDDK · TUFTS UNIVERSITY BOSTON · PI FENG, HANPING · 2007 to 2011
$605k
GENETICS AND ROLE OF ALGINATE IN P. AERUGINOSA INFECTIONR29AI030050 · NIAID · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI GOLDBERG, JOANNA B. · 1991 to 1995
–
NIAID NIH HHS N01 AI030050NIDDK NIH HHS K01 DK076549NIDDK NIH HHS K01DK076549
6 · The paper itself

Abstract

Clostridium difficile causes serious and potentially fatal inflammatory diseases of the colon. Two large protein toxins, TcdA and TcdB, have been clearly implicated in pathogenesis. The goal of this study was to determine whether the glucosyltransferase activity of the toxins is critical for the induction of tumor necrosis factor-alpha (TNF-alpha), an important cytokine mediating both local and systematic inflammatory response. A dose-dependent TNF-alpha secretion was demonstrated in murine macrophage cell line RAW 264.7 after exposure to TcdA or TcdB. TNF-alpha production was blocked by anti-toxin antibodies, indicating that the cytokine-driven response is mediated by the toxins. Both toxins disrupted the cytoskeleton of host cells, while cytoskeleton disruptions using Cytochalasin-D and latrunculin B did not affect TNF-alpha production. The TNF-alpha synthesis was inhibited by reagents that target clathrin-dependent endocytosis or prevent endosomal acidification, suggesting that the endocytosis pathway is necessary for the induction of TNF-alpha. Furthermore, knockout of the enzymatic activity by mutating two key amino acids in the catalytic domain of TcdA abolished its cytokine-inducing activity. Our studies demonstrated a crucial role of the glucosyltransferase activity of C. difficile toxins in the induction of TNF-alpha in macrophages.

Indexed as

AnimalsBacterial ProteinsBacterial ToxinsCell Line, TransformedClostridioides difficileEnterocolitis, PseudomembranousEnterotoxinsMacrophagesMiceTumor Necrosis Factor-alphaBacterial ProteinsBacterial ToxinsEnterotoxinstcdA protein, Clostridium difficiletoxB protein, Clostridium difficileTumor Necrosis Factor-alpha

Identifiers

PMID19324080
PMCPMC2692465
OpenAlexW2066921908

What OpenQuestion holds

Textmetadata
LicenceTDM
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.