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Title: Correlation between in vitro cytotoxicity and in vivo lethal activity in mice of epsilon toxin mutants from Clostridium perfringens
Author: Dorca Arévalo, Jonatan
Pauillac, Serge
Díaz Hidalgo, Laura
Martín Satué, Mireia
Popoff, Michel R.
Blasi Cabús, Joan
Keywords: Membranes cel·lulars
Cèl·lules epitelials
Cell membranes
Epithelial cells
Issue Date: 11-Jul-2014
Publisher: Public Library of Science (PLoS)
Abstract: Epsilon toxin (Etx) from Clostridium perfringens is a pore-forming protein with a lethal effect on livestock, producing severe enterotoxemia characterized by general edema and neurological alterations. Site-specific mutations of the toxin are valuable tools to study the cellular and molecular mechanism of the toxin activity. In particular, mutants with paired cysteine substitutions that affect the membrane insertion domain behaved as dominant-negative inhibitors of toxin activity in MDCK cells. We produced similar mutants, together with a well-known non-toxic mutant (Etx-H106P), as green fluorescent protein (GFP) fusion proteins to perform in vivo studies in an acutely intoxicated mouse model. The mutant (GFP-Etx-I51C/A114C) had a lethal effect with generalized edema, and accumulated in the brain parenchyma due to its ability to cross the blood-brain barrier (BBB). In the renal system, this mutant had a cytotoxic effect on distal tubule epithelial cells. The other mutants studied (GFP-Etx-V56C/F118C and GFP-Etx-H106P) did not have a lethal effect or cross the BBB, and failed to induce a cytotoxic effect on renal epithelial cells. These data suggest a direct correlation between the lethal effect of the toxin, with its cytotoxic effect on the kidney distal tubule cells, and the ability to cross the BBB.
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It is part of: PLoS One, 2014, vol. 9, num. 7
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)

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