Cytotoxicity of the Bacillus cereus Nhe Enterotoxin Requires Specific Binding Order of Its Three Exoprotein Components
| Autor: | Andrea Didier, Maximilian Casteel, Toril Lindbäck, Stefanie Bock, Marianne Sundt Sødring, Carina Nielsen, Annette Fagerlund, Per Einar Granum, Simon P. Hardy, Richard Dietrich, Maximilian Moravek, Erwin Märtlbauer |
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| Rok vydání: | 2010 |
| Předmět: |
Lysis
Immunology Bacillus cereus Priming (immunology) Enterotoxin medicine.disease_cause Microbiology Enterotoxins Chlorocebus aethiops medicine Animals Cytotoxicity Vero Cells Dose-Response Relationship Drug L-Lactate Dehydrogenase biology Toxin biology.organism_classification Molecular Pathogenesis Infectious Diseases Biochemistry Biophysics Vero cell Parasitology Cysteine |
| Zdroj: | Infection and Immunity. 78:3813-3821 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00247-10 |
| Popis: | This study focuses on the interaction of the three components of the Bacillus cereus Nhe enterotoxin with particular emphasis on the functional roles of NheB and NheC. The results demonstrated that both NheB and NheC were able to bind to Vero cells directly while NheA lacked this ability. It was also shown that Nhe-induced cytotoxicity required a specific binding order of the individual components whereby the presence of NheC in the priming step as well as the presence of NheA in the final incubation step was mandatory. Priming of cells with NheB alone and addition of NheA plus NheC in the second step failed to induce toxic effects. Furthermore, in solution, excess NheC inhibited binding of NheB to Vero cells, whereas priming of cells with excess NheC resulted in full toxicity if unbound NheC was removed before addition of NheB. By using mutated NheC proteins where the two cysteine residues in the predicted β-tongue were replaced with glycine (NheC cys− ) or where the entire hydrophobic stretch was deleted (NheC hr− ), the predicted hydrophobic β-tongue of NheC was found essential for binding to cell membranes but not for interaction with NheB in solution. All data presented here are compatible with the following model. The first step in the mode of action of Nhe is associated with binding of NheC and NheB to the cell surface and probably accompanied by conformational changes. These events allow subsequent binding of NheA, leading to cell lysis. |
| Databáze: | OpenAIRE |
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