Journal Article

Reactive Oxygen Species and the MEK/ERK Pathway Are Involved in the Toxicity of <i>Clostridium perfringens</i> α-Toxin, a Prototype Bacterial Phospholipase C

Laura Monturiol-Gross, Marietta Flores-Díaz, Cindy Araya-Castillo, María-José Pineda-Padilla, Graeme C. Clark, Richard W. Titball and Alberto Alape-Girón

in The Journal of Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 206, issue 8, pages 1218-1226
Published in print October 2012 | ISSN: 0022-1899
Published online August 2012 | e-ISSN: 1537-6613 | DOI: http://dx.doi.org/10.1093/infdis/jis496
Reactive Oxygen Species and the MEK/ERK Pathway Are Involved in the Toxicity of Clostridium perfringens α-Toxin, a Prototype Bacterial Phospholipase C

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Clostridium perfringens, the most broadly distributed pathogen in nature, produces a prototype phospholipase C, also called α-toxin, which plays a key role in the pathogenesis of gas gangrene. α-Toxin causes plasma membrane disruption at high concentrations, but the role of intracellular mediators in its toxicity at low concentrations is unknown. This work demonstrates that α-toxin causes oxidative stress and activates the MEK/ERK pathway in cultured cells and furthermore provides compelling evidence that O2−., hydrogen peroxide, and the OH. radical are involved in its cytotoxic and myotoxic effects. The data show that antioxidants and MEK1 inhibitors reduce the cytotoxic and myotoxic effects of α-toxin and demonstrate that edaravone, a clinically used hydroxyl radical trap, reduces the myonecrosis and the mortality caused by an experimental infection with C. perfringens in a murine model of gas gangrene. This knowledge provides new insights for the development of novel therapies to reduce tissue damage during clostridial myonecrosis.

Journal Article.  4688 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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