ArticleInfection and immunity2015
Critical roles of Clostridium difficile toxin B enzymatic activities in pathogenesis.
Article in Infection and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Biliverdin targeting TcdB-DRBD inhibits Clostridioides difficile virulence and restores gut microbiota in Mongolian gerbils (Meriones unguiculatus).Communications biology · 2025Article
- Intestinal Microbiota Dysbiosis Role and Bacterial Translocation as a Factor for Septic Risk.International journal of molecular sciences · 2025Review
- Mechanisms ofFrontiers in cellular and infection microbiology · 2025Review
- De novo design of mini-protein binders broadly neutralizing Clostridioides difficile toxin B variants.Nature communications · 2024Article
- A fine-tuned yeast surface-display/secretion platform enables the rapid discovery of neutralizing antibodies against Clostridioides difficile toxins.Microbial cell factories · 2023Article
- Glucosyltransferase-dependent and independent effects of Clostridioides difficile toxins during infection.PLoS pathogens · 2022Article
- A new dawn for monoclonal antibodies against antimicrobial resistant bacteria.Frontiers in microbiology · 2022Review
- Neutralizing epitopes onFrontiers in immunology · 2022Article
- Structural basis for CSPG4 as a receptor for TcdB and a therapeutic target in Clostridioides difficile infection.Nature communications · 2021Article
- Murine Intrarectal Instillation of Purified RecombinantInfection and immunity · 2021Article
- The glucosyltransferase activity of C. difficile Toxin B is required for disease pathogenesis.PLoS pathogens · 2020Article
- Therapeutic Mechanism of Macrophage Inflammatory Protein 1 α Neutralizing Antibody (CCL3) in Clostridium difficile Infection in Mice.The Journal of infectious diseases · 2020Article
- Structure of the full-length Clostridium difficile toxin B.Nature structural & molecular biology · 2019Article
- The chaperonin TRiC/CCT is essential for the action of bacterial glycosylating protein toxins likeProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Treatment of Clostridium difficile Infection with a Small-Molecule Inhibitor of Toxin UDP-Glucose Hydrolysis Activity.Antimicrobial agents and chemotherapy · 2018Article
- Pathology afterProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Cysteine Protease-Mediated Autocleavage ofCellular and molecular gastroenterology and hepatology · 2018Article
- The role of purified Clostridium difficile glucosylating toxins in disease pathogenesis utilizing a murine cecum injection model.Anaerobe · 2017Article
- The role of toxins in Clostridium difficile infection.FEMS microbiology reviews · 2017Review
- Pathogenic effects of glucosyltransferase from Clostridium difficile toxins.Pathogens and disease · 2016Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
TcdB is one of the key virulence factors of Clostridium difficile that is responsible for causing serious and potentially fatal colitis. The toxin contains at least two enzymatic domains: an effector glucosyltransferase domain for inactivating host Rho GTPases and a cysteine protease domain for the delivery of the effector domain into host cytosol. Here, we describe a novel intrabody approach to examine the role of these enzymes of TcdB in cellular intoxication. By screening a single-domain heavy chain (V(H)H) library raised against TcdB, we identified two V(H)H antibodies, 7F and E3, that specifically inhibit TcdB cysteine protease and glucosyltransferase activities, respectively. Cytoplasmic expression of 7F intrabody in Vero cells inhibited TcdB autoprocessing and delayed cellular intoxication, whereas E3 intrabody completely blocked the cytopathic effects of TcdB holotoxin. These data also demonstrate for the first time that toxin autoprocessing occurs after cysteine protease and glucosyltransferase domains translocate into the cytosol of target cells. We further determined the role of the enzymatic activities of TcdB in in vivo toxicity using a sensitive systemic challenge model in mice. Consistent with these in vitro results, a cysteine protease noncleavable mutant, TcdB-L543A, delayed toxicity in mice, whereas glycosyltransferase-deficient TcdB demonstrated no toxicity up to 500-fold of the 50% lethal dose (LD50) when it was injected systemically. Thus, glucosyltransferase but not cysteine protease activity is critical for TcdB-mediated cytopathic effects and TcdB systemic toxicity, highlighting the importance of targeting toxin glucosyltransferase activity for future therapy.
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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.