Transient expression of RhoA, -B, and -C GTPases in HeLa cells potentiates resistance to Clostridium difficile toxins A and B but not to Clostridium sordellii lethal toxin.

摘要: The bacterial pathogen Clostridium difficle synthesizes two high-molecular-weight toxins (A and B), which exhibit toxic effects in vivo vitro. Here, we present evidence that the major intracellular targets of these are Rho GTPases. Overexpression RhoA, RhoB, or RhoC GTPases transfected HeLa cells conferred an increased resistance to A B, indicating cause their cytopathic primarily by affecting proteins. In addition, toxin B treatment appeared result modification Rho, since isolated from toxin-treated had a decreased ability be ADP-ribosylated botulinum C3 exoenzyme. contrast, lethal (LT) sordellii, although structurally immunologically related C. difficile induce independently RhoA did not protect them effect LT, lysates LT-treated was resistant C3. Immunofluorescence studies showed LT caused very different those described for resulting increase cortical F-actin, with concomitant decrease number stress fibers, formation numerous microvilli containing actin-bundling protein fimbrin/plastin.