Binding of epsilon-toxin from Clostridium perfringens in the nervous system |
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| Authors: | Dorca-Arévalo Jonatan Soler-Jover Alex Gibert Maryse Popoff Michel R Martín-Satué Mireia Blasi Juan |
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| Institution: | Laboratori de Neurobiologia Cel.lular i Molecular, Departament de Patologia i Terapèutica Experimental, Campus de Bellvitge, Universitat de Barcelona-IDIBELL, c/Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Spain. |
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| Abstract: | Epsilon-toxin (varepsilon-toxin), produced by Clostridium perfringens type D, is the main agent responsible for enterotoxaemia in livestock. Neurological disorders are a characteristic of the onset of toxin poisoning. varepsilon-Toxin accumulates specifically in the central nervous system, where it produces a glutamatergic-mediated excitotoxic effect. However, no detailed study of putative binding structures in the nervous tissue has been carried out to date. Here we attempt to identify specific acceptor moieties and cell targets for varepsilon-toxin, not only in the mouse nervous system but also in the brains of sheep and cattle. An varepsilon-toxin-GFP fusion protein was produced and used to incubate brain sections, which were then analyzed by confocal microscopy. The results clearly show specific binding of varepsilon-toxin to myelin structures. varepsilon-Prototoxin-GFP and varepsilon-toxin-GFP, the inactive and active forms of the toxin, respectively, showed identical results. By means of pronase E treatment, we found that the binding was mainly associated to a protein component of the myelin. Myelinated peripheral nerve fibres were also stained by varepsilon-toxin. Moreover, the binding to myelin was not only restricted to rodents, but was also found in humans, sheep and cattle. Curiously, in the brains of both sheep and cattle, the toxin strongly stained the vascular endothelium, a result that may explain the differences in potency and effect between species. Although the binding of varepsilon-toxin to myelin does not directly explain its neurotoxic effect, this feature opens up a new line of enquiry into its mechanism of toxicity and establishes the usefulness of this toxin for the study of the mammalian nervous system. |
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