ArticlePLoS pathogens2020
The glucosyltransferase activity of C. difficile Toxin B is required for disease pathogenesis.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Hyperimmune yolk extract with Immunoglobulin Y basic active principle as a possible adjuvant treatment in patients who need/benefit from neurorehabilitation, withJournal of medicine and life · 2022Pooled it
- The impact of TcdB conformational dynamics on vaccination against Clostridioides difficile.PLoS pathogens · 2026Article
- Clostridioides difficile toxin A and toxin B inhibit toxin-specific adaptive immune responses through glucosyltransferase-dependent activity.Mucosal immunology · 2025Article
- CD44 is a macrophage receptor for TcdB fromGut microbes · 2025Article
- Mechanisms ofFrontiers in cellular and infection microbiology · 2025Review
- Health Hazard Associated with the Presence ofFoods (Basel, Switzerland) · 2024Review
- Genomic and phenotypic studies amongMicrobiology spectrum · 2024Article
- The state of play of rodent models for the study ofJournal of medical microbiology · 2024Review
- Clostridioides difficile toxin B subverts germinal center and antibody recall responses by stimulating a drug-treatable CXCR4-dependent mechanism.Cell reports · 2024Article
- Exploring the Toxin-Mediated Mechanisms inMicroorganisms · 2024Review
- Reviewing theMicroorganisms · 2024Review
- Pathogenicity and virulence ofVirulence · 2023Review
- Nanobodies against C. difficile TcdA and TcdB reveal unexpected neutralizing epitopes and provide a toolkit for toxin quantitation in vivo.PLoS pathogens · 2023Article
- Article
- P2X7 receptor blockade decreases inflammation, apoptosis, and enteric neuron loss duringWorld journal of gastroenterology · 2022Article
- Clostridioides difficile toxins: mechanisms of action and antitoxin therapeutics.Nature reviews. Microbiology · 2022Review
- TcdB ofInternational journal of molecular sciences · 2022Article
- Glucosyltransferase-dependent and independent effects of Clostridioides difficile toxins during infection.PLoS pathogens · 2022Article
- Structural basis for selective modification of Rho and Ras GTPases byScience advances · 2021Article
- Large Clostridial Toxins: Mechanisms and Roles in Disease.Microbiology and molecular biology reviews : MMBR · 2021Review
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Enzymatic inactivation of Rho-family GTPases by the glucosyltransferase domain of Clostridioides difficile Toxin B (TcdB) gives rise to various pathogenic effects in cells that are classically thought to be responsible for the disease symptoms associated with C. difficile infection (CDI). Recent in vitro studies have shown that TcdB can, under certain circumstances, induce cellular toxicities that are independent of glucosyltransferase (GT) activity, calling into question the precise role of GT activity. Here, to establish the importance of GT activity in CDI disease pathogenesis, we generated the first described mutant strain of C. difficile producing glucosyltransferase-defective (GT-defective) toxin. Using allelic exchange (AE) technology, we first deleted tcdA in C. difficile 630Δerm and subsequently introduced a deactivating D270N substitution in the GT domain of TcdB. To examine the role of GT activity in vivo, we tested each strain in two different animal models of CDI pathogenesis. In the non-lethal murine model of infection, the GT-defective mutant induced minimal pathology in host tissues as compared to the profound caecal inflammation seen in the wild-type and 630ΔermΔtcdA (ΔtcdA) strains. In the more sensitive hamster model of CDI, whereas hamsters in the wild-type or ΔtcdA groups succumbed to fulminant infection within 4 days, all hamsters infected with the GT-defective mutant survived the 10-day infection period without primary symptoms of CDI or evidence of caecal inflammation. These data demonstrate that GT activity is indispensable for disease pathogenesis and reaffirm its central role in disease and its importance as a therapeutic target for small-molecule inhibition.
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