The Myelin and Lymphocyte Protein MAL Is Required for Binding and Activity of ε-Toxin

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Clostridium perfringens epsilon-toxin is a potent pore-forming toxin responsible for a devastating central nervous system disease in livestock and has been suggested as a possible environmental trigger for Multiple Sclerosis. Epsilon-toxin binds with great specificity to a restricted number of host cell types and structures, for example gut epithelial cells, blood-brain barrier endothelial cells, and myelin. While most pore-forming toxins achieve binding through specific interaction with respective receptors on the cell membrane, the receptor for epsilon-toxin, however, is unknown. In this report we identify the Myelin and Lymphocyte protein, MAL, as being necessary for binding and cytotoxic effects of epsilon-toxin, and we show its second extracellular loop is critical in this novel function. At a physiological level, mice homozygous for a targeted deletion of the MAL gene lack sensitivity to epsilon-toxin whereas the toxin is lethal in wild-type mice. These observations lead to the possibility that MAL is a candidate receptor for epsilon-toxin. However, we have not demonstrated a physical interaction between epsilon-toxin and MAL.

Vyšlo v časopise: The Myelin and Lymphocyte Protein MAL Is Required for Binding and Activity of ε-Toxin. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004896
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004896

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