The role of toxin A and toxin B in Clostridium difficile infection

By S. Kuehne, Stephen T. Cartman, J. Heap, M. Kelly, A. Cockayne, N. Minton. Nature, 2010

863 citations recorded by the source corpus.

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.

Subfields: Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/f76e3cf5bc42762a9a47f734429f06c74aa967d4

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Citations in the corpus

Consequences of bile salt biotransformations by intestinal bacteria (2016, background): “difficile spores, which germinate in the GI tract producing vegetative cells that secrete toxin A and B causing diarrhea and severe colitis in some cases.(117,118) Patients with antibiotics associated diarrhea and/or colitis are initially treated with either metronidazole or vancomycin to kill C.”
Antibiotics as Major Disruptors of Gut Microbiota (2020, background): “C. difficile produces toxins A and B that can damage the gut mucosa (Kuehne et al., 2010).”