PMID:20844489

Citation	Kuehne, SA, Cartman, ST, Heap, JT, Kelly, ML, Cockayne, A and Minton, NP (2010) The role of toxin A and toxin B in Clostridium difficile infection. Nature 467:711-3
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.
Links	PubMed Online version:10.1038/nature09397
Keywords	Animals; Antibodies, Neutralizing; Bacterial Toxins/antagonists & inhibitors; Bacterial Toxins/genetics; Bacterial Toxins/metabolism; Cercopithecus aethiops; Clostridium Infections/microbiology; Clostridium difficile/classification; Clostridium difficile/genetics; Clostridium difficile/metabolism; Clostridium difficile/pathogenicity; Cricetinae; Disease Models, Animal; Enterotoxins/antagonists & inhibitors; Enterotoxins/genetics; Enterotoxins/metabolism; Gene Deletion; HT29 Cells; Humans; Neutralization Tests; Vero Cells; Virulence/genetics
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
PEPDI:TOXB		GO:0009405 : pathogenesis	ECO:0000315:		P		Figure 2ab utilizes toxin end point titre and cytotoxic effects on Vero and HT29 cells, while figure 2cd measures toxin neutralization assays. Figure 3a measures the time between innoculation and colonization in the hamster specimins between the different mutants. Figure 3b measures the time from colonization to death of the specimins between the different mutant strains.	complete CACAO 3763
PEPDI:TOXB	involved_in	GO:0009405: pathogenesis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

See Help:References for how to manage references in GONUTS.