Correlation between in vitro cytotoxicity and in vivo lethal activity in mice of epsilon toxin mutants from Clostridium perfringens
| Autor: | Dorca Arévalo, Jonatan, Pauillac, Serge, Díaz Hidalgo, Laura, Martín Satué, Mireia, Popoff, Michel R., Blasi Cabús, Joan |
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| Přispěvatelé: | Institut d'Investigació Biomèdica de Bellvitge [Barcelone] ( IDIBELL ), Universitat de Barcelona ( UB ), Bactéries anaérobies et Toxines, Institut Pasteur [Paris], This work was supported by grant SAF2011-27566 (MINECO, Spanish Government) and grant 2009 SGR 152 from AGAUR (Generalitat de Catalunya), The authors thank Inmaculada Gómez de Aranda and the CCiTUB Biology Unit of the Campus de Bellvitge for their technical assistance. We are also grateful to Dr. Mark S. McClain (Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee) for his valuable comments and discussions., Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Universitat de Barcelona (UB), Institut Pasteur [Paris] (IP), Universitat de Barcelona |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Clostridium perfringens Toxicology Mouse models MESH : Green Fluorescent Proteins Madin Darby Canine Kidney Cells MESH: Dogs Mice MESH: Structure-Activity Relationship Membrane proteins Toxin Binding Toxins MESH: Animals Kidney Tubules Distal lcsh:Science MESH: Clostridium perfringens Brain Veterinary Diseases Neurology Medical Microbiology MESH: Epithelial Cells [SDV.TOX]Life Sciences [q-bio]/Toxicology Neurotoxicology MESH : Clostridium perfringens Cell Physiology Multiple Sclerosis MESH: Gene Expression Recombinant Fusion Proteins Primary Cell Culture Immunology Toxic Agents Microbiology Structure-Activity Relationship MESH: Green Fluorescent Proteins MESH: Kidney Tubules Distal MESH: Recombinant Fusion Proteins MESH : Primary Cell Culture Microbial Pathogens [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology lcsh:R Biology and Life Sciences Cell binding Survival Analysis MESH : Kidney Tubules Distal Cell membranes Confocal microscopy MESH : Gene Expression MESH : Brain Mutation Clostridium Infections MESH: Enterotoxemia Veterinary Science lcsh:Q Membranes cel·lulars Veterinary Microbiology [ SDV.TOX ] Life Sciences [q-bio]/Toxicology Veterinary Toxicology Gene Expression lcsh:Medicine Epithelial cells MESH: Blood-Brain Barrier MESH : Blood-Brain Barrier MESH : Dogs Molecular Cell Biology MESH : Structure-Activity Relationship Medicine and Health Sciences Cèl·lules epitelials MESH : Epithelial Cells Blood-Brain Barrier MESH: Survival Analysis MESH : Mutation Research Article MESH: Mutation MESH : Recombinant Fusion Proteins MESH: Biological Transport MESH: Clostridium Infections MESH : Male Bacterial Toxins Green Fluorescent Proteins [SDV.BC]Life Sciences [q-bio]/Cellular Biology Autoimmune Diseases MESH: Primary Cell Culture MESH: Brain Dogs MESH : Mice Animals MESH: Mice MESH : Enterotoxemia MESH : Madin Darby Canine Kidney Cells MESH: Madin Darby Canine Kidney Cells Biological Transport Kidneys Cell Biology Demyelinating Disorders MESH: Male MESH : Clostridium Infections MESH : Biological Transport MESH: Bacterial Toxins Membrane Trafficking Toxines MESH : Bacterial Toxins Clinical Immunology MESH : Animals MESH : Survival Analysis Enterotoxemia |
| Zdroj: | PLoS ONE, Vol 9, Iss 7, p e102417 (2014) PLoS ONE PLoS ONE, Public Library of Science, 2014, 9 (7), pp.e102417. 〈10.1371/journal.pone.0102417〉 PLoS ONE, Public Library of Science, 2014, 9 (7), pp.e102417. ⟨10.1371/journal.pone.0102417⟩ Dipòsit Digital de la UB Universidad de Barcelona PLoS ONE, 2014, 9 (7), pp.e102417. ⟨10.1371/journal.pone.0102417⟩ Recercat. Dipósit de la Recerca de Catalunya instname |
| ISSN: | 1932-6203 |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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