PloS one, 2012-12, Vol.7 (12), p.e51356
2012
Details
- Autor(en) / Beteiligte
- Titel
- CD44 Promotes intoxication by the clostridial iota-family toxins
- Ist Teil von
- PloS one, 2012-12, Vol.7 (12), p.e51356
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2012
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0051356Titel-ID: cdi_plos_journals_1339065422
- Format
- –
- Schlagworte
- Acidification, Actin, ADP Ribose Transferases - toxicity, Animals, Antibodies, Bacterial Toxins - toxicity, Biology, Blotting, Western, Botulinum toxin, CD44 antigen, Cell Line, Tumor, Cell surface, Cells, Cells (Biology), Cellular Biology, Cercopithecus aethiops, Clostridium, Clostridium botulinum, Clostridium perfringens, Cytoskeleton, Cytosol, Cytotoxicity, Dithiothreitol - pharmacology, Dose-Response Relationship, Drug, Endocytosis, Endocytosis - physiology, Endosomes, Enzymes, Hyaluronan Receptors - genetics, Hyaluronan Receptors - metabolism, Immunoprecipitation, Intoxication, Laboratories, Lethality, Life Sciences, Lipids, Mammalian cells, Medicine, Melanoma, Mice, Mice, Knockout, Muscle proteins, Protein binding, Proteins, Proteomics, Toxicity, Toxicology, Toxins, Translocation, Trends, Vero Cells, Viral antibodies