Prevention of the cytopathic effect induced by Clostridium difficile Toxin B by active Rac1.
Clostridium difficile Toxin B (TcdB) glucosylates low molecular weight GTP-binding proteins of the Rho subfamily and thereby causes actin re-organization (cell rounding). This "cytopathic effect" has been generally attributed to RhoA inactivation. Here we show that cells expressing non-glucosylatable Rac1-Q61L are protected from the cytopathic effect of TcdB. In contrast, cells expressing RhoA-Q63L or mock-transfected cells are fully susceptible for the cytopathic effect of TcdB. These findings are extended to the Rac1/RhoG mimic IpgB1 and the RhoA mimic IpgB2 from Shigella. Ectopic expression of IpgB1, but not IpgB2, counteracts the cytopathic effect of TcdB. These data strongly suggest that Rac1 rather than RhoA glucosylation is critical for the cytopathic effect of TcdB.
Halabi-Cabezon
Ismael
I
Institut für Toxikologie, Medizinische Hochschule Hannover, D-30625 Hannover, Germany.
Huelsenbeck
Johannes
J
May
Martin
M
Ladwein
Markus
M
Rottner
Klemens
K
Just
Ingo
I
Genth
Harald
H
D000818:Animals; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D006031:Glycosylation; D051379:Mice; D041681:NIH 3T3 Cells; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D001427:Bacterial Toxins; C031815:toxB protein, Clostridium difficile; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein