ArticleNaunyn-Schmiedeberg's archives of pharmacology2011
Autoproteolytic cleavage mediates cytotoxicity of Clostridium difficile toxin A.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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.
The trial behind it
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Who cites it
32 citing papers in PubMed, 49 citations in OpenAlex.
- Robust high-sensitivity real-time impedance analysis for neutralization drug screening and toxicity kinetics ofFrontiers in microbiology · 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
- Article
- Clostridioides difficile toxins: mechanisms of action and antitoxin therapeutics.Nature reviews. Microbiology · 2022Review
- Activity of Lymphostatin, A Lymphocyte Inhibitory Virulence Factor of Pathogenic Escherichia coli, is Dependent on a Cysteine Protease Motif.Journal of molecular biology · 2021Article
- Large Clostridial Toxins: Mechanisms and Roles in Disease.Microbiology and molecular biology reviews : MMBR · 2021Review
- Structure of the full-length Clostridium difficile toxin B.Nature structural & molecular biology · 2019Article
- The Conserved Cys-2232 inFrontiers in microbiology · 2018Article
- Cysteine Protease-Mediated Autocleavage ofCellular and molecular gastroenterology and hepatology · 2018Article
- The role of toxins in Clostridium difficile infection.FEMS microbiology reviews · 2017Review
- Clostridium difficile Toxins TcdA and TcdB Cause Colonic Tissue Damage by Distinct Mechanisms.Infection and immunity · 2016Article
- Identification of an Essential Region for Translocation of Clostridium difficile Toxin B.Toxins · 2016Article
- Pathogenic effects of glucosyltransferase from Clostridium difficile toxins.Pathogens and disease · 2016Review
- Clostridium difficile Toxins A and B: Insights into Pathogenic Properties and Extraintestinal Effects.Toxins · 2016Review
- Crystal structure of Clostridium difficile toxin A.Nature microbiology · 2016Article
- Review
- A small-molecule antivirulence agent for treating Clostridium difficile infection.Science translational medicine · 2015Article
- Masking autoprocessing of Clostridium difficile toxin A by the C-terminus combined repetitive oligo peptides.Biochemical and biophysical research communications · 2015Article
- The roles of host and pathogen factors and the innate immune response in the pathogenesis of Clostridium difficile infection.Molecular immunology · 2015Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toxin A and toxin B from Clostridium difficile are the causative agents of the antibiotic-associated pseudomembranous colitis. They are of an A/B structure type and possess inositol hexakisphosphate-inducible autoproteolytic activity to release their glucosyltransferase domain to the cytoplasm of target cells. In this study, we investigated the effect of extracellular and intracellular autoproteolytic cleavage on the function of TcdA. Extracellular cleavage led to functional inactivation albeit TcdA was less susceptible to inositol hexakisphosphate-induced autoproteolysis than TcdB. A non-cleavable TcdA mutant (TcdA A541 G542 A543) was generated to investigate whether autoproteolysis is a prerequisite for intracellular function of TcdA. Although the EC(50) regarding cell rounding was about 75-fold reduced in short-term assay, non-cleavable TcdA was able to induce complete cell rounding and apoptosis after 36 h comparable to wildtype TcdA when continuously present. Studies with limited uptake of toxins revealed progressive Rac1 glucosylation and complete cell rounding for TcdA, whereas the effect induced by non-cleavable TcdA was reversible. These findings argue for cytosolic accumulation of the released glucosyltransferase domain of wild-type TcdA and rapid degradation of the non-cleavable TcdA. In summary, extracellular cleavage functionally inactivates TcdA (and TcdB), whereas intracellular autoproteolytic cleavage is not essential for function of TcdA but defines its potency.
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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.