Evidence map›Paper›PMID 32841647›Full record

ArticleGastroenterology2020

Clostridioides difficile Toxin A Remodels Membranes and Mediates DNA Entry Into Cells to Activate Toll-Like Receptor 9 Signaling.

Xinhua Chen, Xiaotong Yang, Jaime de Anda, Jun Huang, Dan Li, Hua Xu, Kelsey S Shields, Mária Džunková, Joshua Hansen, Ishan J Patel and 5 more

Open access · greenAbstract read
In one paragraph

Article in Gastroenterology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.2field-weighted citation impact, top 33% 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

14 citing papers in PubMed, 18 citations in OpenAlex.

  1. SARS-CoV-2 peptide fragments selectively dysregulate specific immune cell populations via Gaussian curvature targeting.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Article
  3. Mechanisms ofFrontiers in cellular and infection microbiology · 2025
    Review
  4. Review
  5. Article
  6. Review
  7. Stool Interleukin-1β Differentiates Clostridioides difficile Infection (CDI) From Asymptomatic Carriage and Non-CDI Diarrhea.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023
    Article
  8. Microbiology (Reading, England) · 2023
    Review
  9. Platelets promote human macrophages-mediated macropinocytosis ofFrontiers in cellular and infection microbiology · 2023
    Article
  10. Article
  11. Article
  12. Amyloid-containing biofilms and autoimmunity.Current opinion in structural biology · 2022
    Review
  13. Review
  14. The Role of Toll-Like Receptor-2 inFrontiers in immunology · 2021
    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

15 authors at 6 institutions in 2 countries.

Xinhua ChenDivision of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. Electronic address: xchen1@bidmc.harvard.edu.
Xiaotong YangDivision of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Institute of Microbiology and Immunology, College of Life Sciences, Shanghai Normal University, Shanghai, China.
Jaime de AndaDepartment of Bioengineering, Department of Chemistry and Biochemistry, California Nano Systems Institute, University of California, Los Angeles, Los Angeles, California.
Jun HuangDivision of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Department of Colorectal Surgery, The 6th Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Dan LiDivision of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Hua XuDivision of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Kelsey S ShieldsDivision of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Mária DžunkováUS Department of Energy Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, California.
Joshua HansenDivision of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Ishan J PatelStony Brook University Hospital, Stony Brook, New York.
Eric U YeeDepartment of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
Douglas T GolenbockDivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts.
Marianne A GrantDivision of Molecular and Vascular Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Gerard C L WongDepartment of Bioengineering, Department of Chemistry and Biochemistry, California Nano Systems Institute, University of California, Los Angeles, Los Angeles, California. Electronic address: gclwong@seas.ucla.edu.
Ciarán P KellyDivision of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Beth Israel Deaconess Medical Center · USCalifornia NanoSystems Institute · USLawrence Berkeley National Laboratory · USStony Brook University Hospital · USUniversity of Arkansas for Medical Sciences · USUniversity of Massachusetts Chan Medical School · US

Funding

X-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6M
Cathelicidins in Skin ImmunityR01AI052453 · NIAID · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · PI GALLO, RICHARD L, NIZET, VICTOR · 2002 to 2017
$5.3M
Ultrasensitive C.difficile toxin measurement for diagnosis and outcome predictionR01AI116596 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI POLLOCK, NIRA · 2016 to 2020
$4.1M
Surface sensing, memory, and motility control in biofilm formationR01AI143730 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI O'TOOLE, GEORGE A., WONG, GERARD C · 2019 to 2023
$2.0M
Combination Clostridium Difficile Toxin and Adhesin VaccineR01AI095256 · NIAID · AARON DIAMOND AIDS RESEARCH CENTER · PI HO, DAVID D, KELLY, CIARAN P · 2012 to 2015
$1.3M
NIAID NIH HHS R01 AI052453NIAID NIH HHS R01 AI095256NIAID NIH HHS R01 AI116596NIAID NIH HHS R01 AI143730NIGMS NIH HHS P41 GM103393
6 · The paper itself

Abstract

BACKGROUND &

aimsClostridioides difficile toxin A (TcdA) activates the innate immune response. TcdA co-purifies with DNA. Toll-like receptor 9 (TLR9) recognizes bacterial DNA to initiate inflammation. We investigated whether DNA bound to TcdA activates an inflammatory response in murine models of C difficile infection via activation of TLR9.

methodsWe performed studies with human colonocytes and monocytes and macrophages from wild-type and TLR9 knockout mice incubated with TcdA or its antagonist (ODN TTAGGG) or transduced with vectors encoding TLR9 or small-interfering RNAs. Cytokine production was measured with enzyme-linked immunosorbent assay. We studied a transduction domain of TcdA (TcdA

resultsThe TcdA

conclusionsTcdA from C difficile can bind and organize bacterial DNA to activate TLR9. TcdA and TcdA fragments remodel membranes, which allows them to access endosomes and present bacterial DNA to and activate TLR9. Rather than inactivating the ability of DNA to bind TLR9, TcdA appears to chaperone and organize DNA into an inflammatory, spatially periodic structure.

Indexed as

AnimalsAnti-Bacterial AgentsBacterial ToxinsClostridioides difficileClostridium InfectionsColitisDisease Models, AnimalDNA, BacterialEnterotoxinsFemaleGastrointestinal MicrobiomeHumansImmunity, InnateMiceMice, KnockoutMolecular ChaperonesAnti-Bacterial AgentsBacterial ToxinsDNA, BacterialEnterotoxinsMolecular ChaperonestcdA protein, Clostridium difficileTlr9 protein, mouseToll-Like Receptor 9Antibiotic-Associated Diarrhea and ColitisIntestinal InflammationPore FormationSAXS

Identifiers

PMID32841647
PMCPMC8720510
OpenAlexW3081131393

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.