R-Ras Glucosylation and Transient RhoA Activation Determine the Cytopathic Effect Produced by Toxin B Variants from Toxin A-negative Strains of Clostridium difficile
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| Autoři: | , , , , , |
|---|---|
| Médium: | artículo |
| Datum vydání: | 2003 |
| Popis: | Clostridium difficile induces antibiotic-associated di-arrhea through the production of toxin A and toxin B;the former toxin has been assumed to be responsible forthe symptoms of the disease. Several toxin A-negativestrains fromC. difficilehave recently been isolated fromclinical cases and have been reported to produce toxin Bvariants eliciting an atypical cytopathic effect. Ultra-structural analysis indicated these toxins induce arounding cytopathic effect and filopodia-like structures.Toxin B variants glucosylated R-Ras, and transfectionwith a constitutively active mutant of this GTPase pro-tected cells against their cytopathic effect. Treatment ofcells with toxin B variants induced detachment from theextracellular matrix and blockade of the epidermalgrowth factor-mediated phosphorylation of extracellu-lar-regulated protein kinases, demonstrating a deleteri-ous effect on the R-Ras-controlled avidity of integrins.Treatment with toxin B variants also induced a tran-sient activation of RhoA probably because of inactiva-tion of Rac1. Altogether, these data indicate that thecytopathic effect induced by toxin B variants is becauseof cell rounding and detachment mediated by R-Ras glu-cosylation, and the induction of filopodia-like struc-tures is mediated by RhoA activation. Implications forthe pathophysiology ofC. difficile-induced diarrhea arediscussed. |
| Země: | Repositorio UNA |
| Instituce: | Universidad Nacional de Costa Rica |
| Repositorio: | Repositorio UNA |
| Jazyk: | Inglés |
| OAI Identifier: | oai:null:11056/17574 |
| On-line přístup: | http://hdl.handle.net/11056/17574 |
| Klíčové slovo: | CLOSTRIDIUM DIFFICILE R-RAS GLUCOSYLATION TOXINAS TOXIN A TOXIN B |