The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
The role of toxin A and toxin B in Clostridium difficile infection
Abstract
Clostridium difficile infection is the leading cause of healthcare-associated diarrhoea in Europe and North America. During infection, C. difficile produces two key virulence determinants, toxin A and toxin B. Experiments with purified toxins have indicated that toxin A alone is able to evoke the symptoms of C. difficile infection, but toxin B is unable to do so unless it is mixed with toxin A or there is prior damage to the gut mucosa. However, a recent study indicated that toxin B is essential for C. difficile virulence and that a strain producing toxin A alone was avirulent. This creates a paradox over the individual importance of toxin A and toxin B. Here we show that isogenic mutants of C. difficile producing either toxin A or toxin B alone can cause fulminant disease in the hamster model of infection. By using a gene knockout system to inactivate the toxin genes permanently, we found that C. difficile producing either one or both toxins showed cytotoxic activity in vitro that translated directly into virulence in vivo. Furthermore, by constructing the first ever double-mutant strain of C. difficile, in which both toxin genes were inactivated, we were able to completely attenuate virulence. Our findings re-establish the importance of both toxin A and toxin B and highlight the need to continue to consider both toxins in the development of diagnostic tests and effective countermeasures against C. difficile.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589
Clostridium difficile Toxins: Mechanism of Action and Role in Disease
Voth, D. E., & Ballard, J. D. (2005) · Clinical Microbiology Reviews · doi:10.1128/cmr.18.2.247-263.2005 · Cited by 1,104
The multidrug-resistant human pathogen Clostridium difficile has a highly mobile, mosaic genome
Sebaihia, M., Wren, B. W., Mullany, P., Fairweather, N. F., Minton, N., Stabler, R., Thomson, N. R., Roberts, A. P., Cerdeño-Tárraga, A. M., Wang, H., et al. (2006) · Nature Genetics · doi:10.1038/ng1830 · Cited by 879
Self-citationToxin B is essential for virulence of Clostridium difficile
Lyras, D., O’Connor, J. R., Howarth, P. M., Sambol, S. P., Carter, G. P., Phumoonna, T., Poon, R., Adams, V., Vedantam, G., Johnson, S., et al. (2009) · Nature · doi:10.1038/nature07822 · Cited by 745
Bile Salts and Glycine as Cogerminants for Clostridium difficile Spores
Sorg, J. A., & Sonenshein, A. L. (2008) · Journal of Bacteriology · doi:10.1128/jb.01765-07 · Cited by 711
The ClosTron: a universal gene knock-out system for the genus Clostridium
Heap, J. T., Pennington, O. J., Cartman, S. T., Carter, G. P., & Minton, N. P. (2007) · Journal of Microbiological Methods · doi:10.1016/j.mimet.2007.05.021 · Cited by 663
Self-citationA modular system for Clostridium shuttle plasmids
Heap, J. T., Pennington, O. J., Cartman, S. T., & Minton, N. P. (2009) · Journal of Microbiological Methods · doi:10.1016/j.mimet.2009.05.004 · Cited by 489
Self-citationThe ClosTron: mutagenesis in Clostridium refined and streamlined
Heap, J. T., Kuehne, S. A., Ehsaan, M., Cartman, S. T., Cooksley, C. M., Scott, J. C., & Minton, N. P. (2010) · Journal of Microbiological Methods · doi:10.1016/j.mimet.2009.10.018 · Cited by 418
Self-citationClostridium difficile-associated diarrhea in adults
Poutanen, S. M. (2004) · Canadian Medical Association Journal · doi:10.1503/cmaj.1031189 · Cited by 410
Effects of Clostridium difficile toxins given intragastrically to animals
Lyerly, D. M., Saum, K. E., MacDonald, D. K., & Wilkins, T. D. (1985) · Infection and Immunity · doi:10.1128/iai.47.2.349-352.1985 · Cited by 400
Cited by
Hypoalbuminemia as Surrogate and Culprit of Infections
Wiedermann, C. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094496 · Cited by 394
Fachi, J. L., Felipe, J. D. S., Pral, L. P., da Silva, B. K., Corrêa, R. O., de Andrade, M. C. P., da Fonseca, D. M., Basso, P. J., Câmara, N. O. S., de Sales e Souza, É. L., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.03.054 · Cited by 364
Thanissery, R., Winston, J. A., & Theriot, C. M. (2017) · Anaerobe · doi:10.1016/j.anaerobe.2017.03.004 · Cited by 242
Biology of Clostridium difficile: Implications for Epidemiology and Diagnosis
Karen C., C., & John G., B. (2011) · Annual Review of Microbiology · doi:10.1146/annurev-micro-090110-102824 · Cited by 233
Clostridioides difficile toxins: mechanisms of action and antitoxin therapeutics
Kordus, S. L., Thomas, A. K., & Lacy, D. B. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-021-00660-2 · Cited by 204
Metadata
- Authors
- Kuehne, S. A., Cartman, S. T., Heap, J. T., Kelly, M. L., Cockayne, A., & Minton, N. P.
- Venue
- Nature
- Published
- 2010-09-15
- Volume
- 467
- Issue
- 7316
- Pages
- 711-713
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2127067932
- Cited by
- 855
- References
- 23
- FWCI
- 39.58
- Type
- journal article
- Language
- en
- Open access
- closed
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: The role of toxin A and toxin B in Clostridium difficile infection. https://app.cochat.ai/papers/10.1038/nature09397
- The paper
- Kuehne, S. A., Cartman, S. T., Heap, J. T., Kelly, M. L., Cockayne, A., & Minton, N. P. (2010). The role of toxin A and toxin B in Clostridium difficile infection. Nature. https://doi.org/10.1038/nature09397
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
