CD44 Promotes Intoxication by the Clostridial Iota-Family Toxins
| Autor: | Wigelsworth, Darran, Gordon Ruthel, Schnell, Leonie, Herrlich, Peter, Blonder, Josip, Veenstra, Timothy, Carman, Robert, Wilkins, Tracy, Nhieu, Guy Tran, Pauillac, Serge, Gibert, Maryse, Sauvonnet, Nathalie, Stiles, Bradley, Popoff, Michel, Barth, Holger, Tran, Guy, Nhieu, Van, Chaves-Olarte, Esteban |
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| Přispěvatelé: | Army Medical Research Institute of Infectious Diseases [USA] (USAMRIID), University of Pennsylvania School of Veterinary Medicine, Universität Ulm - Ulm University [Ulm, Allemagne], Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Leibniz Association, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), TechLab Inc, Collège de France (CdF), Bactéries anaérobies et Toxines, Institut Pasteur [Paris], Biologie des Interactions Cellulaires, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Wilson College, Programa de Investigación en Enfermedades Tropicales, UNIVERSIDAD NACIONAL-Escuela de Medicina Veterinaria, Funding was provided in part by the Institut Pasteur (MRP), Faculty Fund for Research at Wilson College (BGS), as well as the Faculty of Medicine at the University of Ulm plus Deutsche Forschungsgemeinschaft (DFG grant BA 2087/2-1) to HB, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie des Interactions Cellulaires (BIC), U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Army Medical Research Institute of Infectious Diseases, Medical Research Institute, University of Ulm, Leibniz Institute for Age Research, Fritz Lipmann Institute, National Cancer Institute ( NIH ), Collège de France ( CdF ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Bacterial Diseases
Mouse Clostridium spiroforme Cytotoxicity [ SDV.TOX ] Life Sciences [q-bio]/Toxicology lcsh:Medicine Pathogenesis medicine.disease_cause Biochemistry Mice Clostridium AB toxin Chlorocebus aethiops Clostridium botulinum Toxins lcsh:Science ADP Ribose Transferases Mice Knockout 0303 health sciences Multidisciplinary biology Animal Models Clostridium difficile Endocytosis Recombinant Proteins Bacterial Pathogens 3. Good health Hyaluronan Receptors Infectious Diseases Medical Microbiology [SDV.TOX]Life Sciences [q-bio]/Toxicology Medicine Vero cells Research Article Bacterial Toxins Blotting Western Intoxication [SDV.BC]Life Sciences [q-bio]/Cellular Biology Microbiology 03 medical and health sciences Model Organisms Cell Line Tumor medicine Animals Immunoprecipitation Protein Interactions Biology 030304 developmental biology Gram Positive Dose-Response Relationship Drug [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology 030306 microbiology Toxin lcsh:R Proteins CD coreceptors biology.organism_classification Actin cytoskeleton Dithiothreitol Cytoskeletal Proteins lcsh:Q |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2012, 7 (12), pp.e51356. ⟨10.1371/journal.pone.0051356⟩ BASE-Bielefeld Academic Search Engine PLoS ONE, Vol 7, Iss 12, p e51356 (2012) PLoS ONE, 2012, 7 (12), pp.e51356. ⟨10.1371/journal.pone.0051356⟩ PLoS ONE, Public Library of Science, 2012, 7 (12), pp.e51356. 〈10.1371/journal.pone.0051356〉 |
| ISSN: | 1932-6203 |
| Popis: | International audience; Various pathogenic clostridia produce binary protein toxins associated with enteric diseases of humans and animals. Separate binding/translocation (B) components bind to a protein receptor on the cell surface, assemble with enzymatic (A) component(s), and mediate endocytosis of the toxin complex. Ultimately there is translocation of A component(s) from acidified endosomes into the cytosol, leading to destruction of the actin cytoskeleton. Our results revealed that CD44, a multifunctional surface protein of mammalian cells, facilitates intoxication by the iota family of clostridial binary toxins. Specific antibody against CD44 inhibited cytotoxicity of the prototypical Clostridium perfringens iota toxin. Versus CD44(+) melanoma cells, those lacking CD44 bound less toxin and were dose-dependently resistant to C. perfringens iota, as well as Clostridium difficile and Clostridium spiroforme iota-like, toxins. Purified CD44 specifically interacted in vitro with iota and iota-like, but not related Clostridium botulinum C2, toxins. Furthermore, CD44 knockout mice were resistant to iota toxin lethality. Collective data reveal an important role for CD44 during intoxication by a family of clostridial binary toxins. |
| Databáze: | OpenAIRE |
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