Clostridium difficile toxins: more than mere inhibitors of Rho proteins.
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.
Genth
Harald
H
Institut für Toxikologie, Medizinische Hochschule Hannover, D-30625 Hannover, Germany. genth.harald@mh-hannover.de
Dreger
Stefanie C
SC
Huelsenbeck
Johannes
J
Just
Ingo
I
D017209:Apoptosis / Q000187:drug effects; D001426:Bacterial Proteins / Q000378:metabolism / Q000494:pharmacology; D001427:Bacterial Toxins / Q000378:metabolism* / Q000494:pharmacology; D016360:Clostridioides difficile / Q000378:metabolism*; D004768:Enterotoxins / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; D020741:rho GTP-Binding Proteins