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Int J Biochem Cell Biol. 2008;40(4):592-7. doi: 10.1016/j.biocel.2007.12.014. Epub 2008 Jan 5.

Clostridium difficile toxins: more than mere inhibitors of Rho proteins.

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Institut für Toxikologie, Medizinische Hochschule Hannover, D-30625 Hannover, Germany.


Toxin A (TcdA) and Toxin B (TcdB) are the major pathogenicity factors of the Clostridium difficile-associated diarrhoea (CDAD). The single-chained protein toxins enter their target cells by receptor-mediated endocytosis. New data show the critical role of auto-catalytic processing for target cell entry. Inside the cell, the toxins mono-glucosylate and thereby inactivate low molecular mass GTP-binding proteins of the Rho subfamily. Toxin-treated cells respond to RhoA glucosylation with up-regulation and activation of the pro-apoptotic Rho family protein RhoB. These data reinforce the critical role of the glucosyltransferase activity for programmed cell death and show that TcdA and TcdB, generally classified as broad-spectrum inhibitors of Rho proteins, are also capable of activating Rho proteins.

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