Evidence map›Paper›PMID 27456833›Full record

ArticleInfection and immunity2016

Clostridium difficile Toxins TcdA and TcdB Cause Colonic Tissue Damage by Distinct Mechanisms.

Nicole M Chumbler, Melissa A Farrow, Lynne A Lapierre, Jeffrey L Franklin, D Borden Lacy

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

49 citing papers in PubMed, 72 citations in OpenAlex.

  1. Article
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  17. Pro-Inflammatory Cytokines Enhanced In Vitro Cytotoxic Activity ofInternational journal of molecular sciences · 2024
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  18. Review
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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 1 country.

Nicole M ChumblerDepartment of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Melissa A FarrowDepartment of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Lynne A LapierreDepartment of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee, USA The Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA Epithelial Biology Center, Vanderbilt University, Nashville, Tennessee, USA.
Jeffrey L FranklinDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA The Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA Epithelial Biology Center, Vanderbilt University, Nashville, Tennessee, USA.
D Borden LacyDepartment of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA The Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA borden.lacy@vanderbilt.edu.
VA Tennessee Valley Healthcare System · USVanderbilt University · US

Funding

Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
Structural mechanisms of Clostridium difficile pathogenesisR01AI095755 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI LACY, DANA BORDEN · 2011 to 2020
$3.9M
Structural Mechanisms of Clostridioides difficile pathogenesisR37AI095755 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Dana Borden Lacy · 2021 to 2026
$3.2M
The role of toxins in Clostridium difficile infection pathogenesisI01BX002943 · VA · VETERANS HEALTH ADMINISTRATION · PI LACY, DANA BORDEN · 2016 to 2025
–
BLRD VA I01 BX002943NIAID NIH HHS R01 AI095755NIAID NIH HHS R37 AI095755NIDDK NIH HHS P30 DK058404
6 · The paper itself

Abstract

As the major cause of antibiotic-associated diarrhea, Clostridium difficile is a serious problem in health care facilities worldwide. C. difficile produces two large toxins, TcdA and TcdB, which are the primary virulence factors in disease. The respective functions of these toxins have been difficult to discern, in part because the cytotoxicity profiles for these toxins differ with concentration and cell type. The goal of this study was to develop a cell culture model that would allow a side-by-side mechanistic comparison of the toxins. Conditionally immortalized, young adult mouse colonic (YAMC) epithelial cells demonstrate an exquisite sensitivity to both toxins with phenotypes that agree with observations in tissue explants. TcdA intoxication results in an apoptotic cell death that is dependent on the glucosyltransferase activity of the toxin. In contrast, TcdB has a bimodal mechanism; it induces apoptosis in a glucosyltransferase-dependent manner at lower concentrations and glucosyltransferase-independent necrotic death at higher concentrations. The direct comparison of the responses to TcdA and TcdB in cells and colonic explants provides the opportunity to unify a large body of observations made by many independent investigators.

Indexed as

Analysis of VarianceAnimalsApoptosisBacterial ToxinsCell DeathCells, CulturedClostridioides difficileColonEnterotoxinsEpithelial CellsGlucosyltransferasesMiceBacterial ToxinsEnterotoxinsGlucosyltransferases

Identifiers

PMID27456833
PMCPMC5038081
OpenAlexW2493899884

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.