ArticleMolecular microbiology2012
TcdB from hypervirulent Clostridium difficile exhibits increased efficiency of autoprocessing.
Article in Molecular microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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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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.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- Substance P receptor blockade is associated with increased survival of patients withbioRxiv : the preprint server for biology · 2026Article
- Large Clostridial Toxins: A Brief Review and Insights into Antigen Design for Veterinary Vaccine Development.Molecular biotechnology · 2025Review
- Mechanisms ofFrontiers in cellular and infection microbiology · 2025Review
- A sequence invariable region in TcdB2 is required for toxin escape fromJournal of bacteriology · 2024Article
- Large Clostridial Toxins: Mechanisms and Roles in Disease.Microbiology and molecular biology reviews : MMBR · 2021Review
- Functional analyses of epidemic Clostridioides difficile toxin B variants reveal their divergence in utilizing receptors and inducing pathology.PLoS pathogens · 2021Article
- Subtyping analysis reveals new variants and accelerated evolution of Clostridioides difficile toxin B.Communications biology · 2020Article
- Structure of the full-length Clostridium difficile toxin B.Nature structural & molecular biology · 2019Article
- Toxin B Variants fromToxins · 2019Article
- A neutralizing antibody that blocks delivery of the enzymatic cargo ofThe Journal of biological chemistry · 2018Article
- The Conserved Cys-2232 inFrontiers in microbiology · 2018Article
- Cysteine Protease-Mediated Autocleavage ofCellular and molecular gastroenterology and hepatology · 2018Article
- On and Off: A Dual Role for Cysteine Protease Autoprocessing ofCellular and molecular gastroenterology and hepatology · 2018Article
- Clostridium difficile colitis: pathogenesis and host defence.Nature reviews. Microbiology · 2016Review
- Clostridium difficile infection.Nature reviews. Disease primers · 2016Review
- Variation in germination of Clostridium difficile clinical isolates correlates to disease severity.Anaerobe · 2015Article
- Masking autoprocessing of Clostridium difficile toxin A by the C-terminus combined repetitive oligo peptides.Biochemical and biophysical research communications · 2015Article
- Exposure of neutralizing epitopes in the carboxyl-terminal domain of TcdB is altered by a proximal hypervariable region.The Journal of biological chemistry · 2015Article
- Critical roles of Clostridium difficile toxin B enzymatic activities in pathogenesis.Infection and immunity · 2015Article
- Variations in virulence and molecular biology among emerging strains of Clostridium difficile.Microbiology and molecular biology reviews : MMBR · 2013Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
TcdB, an intracellular bacterial toxin that inactivates small GTPases, is a major Clostridium difficile virulence factor. Recent studies have found that TcdB produced by emerging/hypervirulent strains of C. difficile is more potent than TcdB from historical strains, and in the current work, studies were performed to investigate the underlying mechanisms for this change in TcdB toxicity. Using a series of biochemical analyses we found that TcdB from a hypervirulent strain (TcdB(HV) ) was more efficient at autoprocessing than TcdB from a historical strain (TcdB(HIST) ). TcdB(HV) and TcdB(HIST) were activated by similar concentrations of IP6; however, the overall efficiency of processing was 20% higher for TcdB(HV) . Using an activity-based fluorescent probe (AWP19) an intermediate, activated but uncleaved, form of TcdB(HIST) was identified, while only a processed form of TcdB(HV) could be detected under the same conditions. Using a much higher concentration (200 µM) of the probe revealed an activated uncleaved form of TcdB(HV) , indicating a preferential and more efficient engagement of intramolecular substrate than TcdB(HIST) . Furthermore, a peptide-based inhibitor (Ac-GSL-AOMK) was found to block the cytotoxicity of TcdB(HIST) at a lower concentration than required to inhibit TcdB(HV) . These findings suggest that TcdB(HV) may cause increased cytotoxicity due to more efficient autoprocessing.
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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.