ArticlePLoS pathogens2022
Glucosyltransferase-dependent and independent effects of Clostridioides difficile toxins during infection.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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.
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Who cites it
25 citing papers in PubMed, 29 citations in OpenAlex.
- From colonization to infection: Genomic evolution of Clostridioides difficile pathogenesis.Cell reports · 2026Review
- A programmed reset mechanism primesScience advances · 2026Article
- Phase variable colony morphotypes ofInfection and immunity · 2026Article
- Article
- Modeling Clostridioides difficile toxin pathogenesis and antiserum protection in an immunocompetent intestine-on-chip platform.Scientific reports · 2026Article
- Phase variable colony morphotypes ofbioRxiv : the preprint server for biology · 2026Article
- Clostridioides difficile toxin A and toxin B inhibit toxin-specific adaptive immune responses through glucosyltransferase-dependent activity.Mucosal immunology · 2025Article
- The monoclonal antibody AZD5148 confers broad protection against TcdB-diverse Clostridioides difficile strains in mice.PLoS pathogens · 2025Article
- Mechanisms of bacterial host-to-host transmission.Microbiology and molecular biology reviews : MMBR · 2025Review
- A targeted cell lysis mechanism facilitates toxin release in Clostridioides difficile.bioRxiv : the preprint server for biology · 2025Article
- Article
- The role of the enteric nervous system in the pathogenesis of Clostridioides difficile infection.Nature reviews. Gastroenterology & hepatology · 2025Review
- Clostridioides difficile meets the adenosine system: the art of manipulating host homeostasis.Journal of biomedical science · 2025Review
- Article
- Mechanisms ofFrontiers in cellular and infection microbiology · 2025Review
- Purified CDT toxins and a clean deletion within the CDT locus provide novel insights into the contribution of binary toxin in cellular inflammation and Clostridioides difficile infection.PLoS pathogens · 2024Article
- PhosphoLipidome Alteration Induced byCells · 2024Article
- Exploring the Toxin-Mediated Mechanisms inMicroorganisms · 2024Review
- Pro-Inflammatory Cytokines Enhanced In Vitro Cytotoxic Activity ofInternational journal of molecular sciences · 2024Article
- Nanobodies against C. difficile TcdA and TcdB reveal unexpected neutralizing epitopes and provide a toolkit for toxin quantitation in vivo.PLoS pathogens · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Clostridioides difficile infection (CDI) is the leading cause of nosocomial diarrhea and pseudomembranous colitis in the USA. In addition to these symptoms, patients with CDI can develop severe inflammation and tissue damage, resulting in life-threatening toxic megacolon. CDI is mediated by two large homologous protein toxins, TcdA and TcdB, that bind and hijack receptors to enter host cells where they use glucosyltransferase (GT) enzymes to inactivate Rho family GTPases. GT-dependent intoxication elicits cytopathic changes, cytokine production, and apoptosis. At higher concentrations TcdB induces GT-independent necrosis in cells and tissue by stimulating production of reactive oxygen species via recruitment of the NADPH oxidase complex. Although GT-independent necrosis has been observed in vitro, the relevance of this mechanism during CDI has remained an outstanding question in the field. In this study we generated novel C. difficile toxin mutants in the hypervirulent BI/NAP1/PCR-ribotype 027 R20291 strain to test the hypothesis that GT-independent epithelial damage occurs during CDI. Using the mouse model of CDI, we observed that epithelial damage occurs through a GT-independent process that does not involve immune cell influx. The GT-activity of either toxin was sufficient to cause severe edema and inflammation, yet GT activity of both toxins was necessary to produce severe watery diarrhea. These results demonstrate that both TcdA and TcdB contribute to disease pathogenesis when present. Further, while inactivating GT activity of C. difficile toxins may suppress diarrhea and deleterious GT-dependent immune responses, the potential of severe GT-independent epithelial damage merits consideration when developing toxin-based therapeutics against CDI.
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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.