R-Ras Glucosylation and transient RhoA activation determine the cytopathic effect produced by Toxin B variants from Toxin A-negative strains of clostridium difficile


Saved in:
Bibliographic Details
Authors: Chaves-Olarte, Esteban, Freer, Enrique, Parra, Andrea, Guzman-Verri, Caterina, Moreno, Edgardo, Thelestam, Mónica
Format: artículo
Publication Date:2003
Description:Clostridium difficile induces antibiotic-associated diarrhea through the production of toxin A and toxin B; the former toxin has been assumed to be responsible for the symptoms of the disease. Several toxin A-negative strains from C. difficile have recently been isolated from clinical cases and have been reported to produce toxin B variants eliciting an atypical cytopathic effect. Ultrastructural analysis indicated these toxins induce a rounding cytopathic effect and filopodia-like structures. Toxin B variants glucosylated R-Ras, and transfection with a constitutively active mutant of this GTPase protected cells against their cytopathic effect. Treatment of cells with toxin B variants induced detachment from the extracellular matrix and blockade of the epidermal growth factor-mediated phosphorylation of extracellular-regulated protein kinases, demonstrating a deleterious effect on the R-Ras-controlled avidity of integrins. Treatment with toxin B variants also induced a transient activation of RhoA probably because of inactivation of Rac1. Altogether, these data indicate that the cytopathic effect induced by toxin B variants is because of cell rounding and detachment mediated by R-Ras glucosylation, and the induction of filopodia-like structures is mediated by RhoA activation. Implications for the pathophysiology of C. difficile-induced diarrhea are discussed.
Country:Repositorio UNA
Institution:Universidad Nacional de Costa Rica
Repositorio:Repositorio UNA
OAI Identifier:oai:https://repositorio.una.ac.cr:11056/18426
Online Access:http://hdl.handle.net/11056/18426
Access Level:acceso abierto