ArticlePLoS pathogens2012
Clostridium difficile Toxin B causes epithelial cell necrosis through an autoprocessing-independent mechanism.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 89 papers.
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.
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.
Who cites it
89 citing papers in PubMed, 125 citations in OpenAlex.
- Bacterial probiotics as an aid in the control of Clostridium difficile disease in neonatal pigs.The Canadian veterinary journal = La revue veterinaire canadienne · 2016Trial
- The impact of TcdB conformational dynamics on vaccination against Clostridioides difficile.PLoS pathogens · 2026Article
- Carbadox, a veterinary growth promoter exhibits anticlostridial activity through induction of oxidative stress in Clostridioides difficile.Gut pathogens · 2026Article
- Article
- Ionomycin Exhibits Potent and Selective Bactericidal Activity Against Clostridioides difficile Through Calcium-Dependent Membrane Disruption.MicrobiologyOpen · 2026Article
- Modeling Clostridioides difficile toxin pathogenesis and antiserum protection in an immunocompetent intestine-on-chip platform.Scientific reports · 2026Article
- HumanbioRxiv : the preprint server for biology · 2025Article
- CD44 is a macrophage receptor for TcdB fromGut microbes · 2025Article
- Epitope Conservation of AZD5148, a Broadly Neutralizing Anti-Toxin B Monoclonal Antibody, Among Diverse and Global Contemporary Clostridioides difficile Isolates.The Journal of infectious diseases · 2025Article
- The emerging view on the roles of butyrate inInfection and immunity · 2025Review
- Large Clostridial Toxins: A Brief Review and Insights into Antigen Design for Veterinary Vaccine Development.Molecular biotechnology · 2025Review
- Cysteine proteases and how YabG fits into clan CD of the MEROPS database.Journal of bacteriology · 2025Review
- Community-AcquiredInternational journal of molecular sciences · 2025Review
- Article
- Mechanisms ofFrontiers in cellular and infection microbiology · 2025Review
- Exploring the Toxin-Mediated Mechanisms inMicroorganisms · 2024Review
- Reviewing theMicroorganisms · 2024Review
- Structural dynamics of the CROPs domain control stability and toxicity of Paeniclostridium sordellii lethal toxin.Nature communications · 2023Article
- Polyamines and hypusination are important forInfection and immunity · 2023Article
- Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedHaslam, David [corrected to Haslam, David B]
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Clostridium difficile is the most common cause of antibiotic-associated nosocomial infection in the United States. C. difficile secretes two homologous toxins, TcdA and TcdB, which are responsible for the symptoms of C. difficile associated disease. The mechanism of toxin action includes an autoprocessing event where a cysteine protease domain (CPD) releases a glucosyltransferase domain (GTD) into the cytosol. The GTD acts to modify and inactivate Rho-family GTPases. The presumed importance of autoprocessing in toxicity, and the apparent specificity of the CPD active site make it, potentially, an attractive target for small molecule drug discovery. In the course of exploring this potential, we have discovered that both wild-type TcdB and TcdB mutants with impaired autoprocessing or glucosyltransferase activities are able to induce rapid, necrotic cell death in HeLa and Caco-2 epithelial cell lines. The concentrations required to induce this phenotype correlate with pathology in a porcine colonic explant model of epithelial damage. We conclude that autoprocessing and GTD release is not required for epithelial cell necrosis and that targeting the autoprocessing activity of TcdB for the development of novel therapeutics will not prevent the colonic tissue damage that occurs in C. difficile - associated disease.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.