Toxicology (Amsterdam), 2003-05, Vol.187 (2), p.229-238
2003
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Toxicity of the staphylococcal enterotoxin B mutants with histidine-to-tyrosine substitutions
- Ist Teil von
- Toxicology (Amsterdam), 2003-05, Vol.187 (2), p.229-238
- Ort / Verlag
- Shannon: Elsevier Ireland Ltd
- Erscheinungsjahr
- 2003
- Quelle
- Elsevier ScienceDirect Journals
- Beschreibungen/Notizen
- In this study we made a series of site-directed mutants of staphylococcal enterotoxin B (SEB), in which histidine residues in the molecule were replaced by tyrosine. The mutant genes were cloned and expressed, and the corresponding proteins were purified. These mutant proteins were tested for binding to human HLA-DR4 and for mitogenetic activity in mouse splenocyte culture. Toxicity of the proteins in vivo was evaluated in the actinomycin D-primed C3H/HeJ mouse model. We found that SEB mutant proteins with fewer than four histidine-to-tyrosine (his-to-tyr) substitutions retained toxic properties similar to wild-type SEB. However, studies showed that his-to-tyr substitution of four consecutive histidine residues eliminated SEB toxicity. Our results clearly show that this genetically modified SEB protein is non-toxic and justifies its further development as a component of a new, safer vaccine to prevent SEB intoxication.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0300-483XeISSN: 1879-3185DOI: 10.1016/S0300-483X(03)00049-0Titel-ID: cdi_proquest_miscellaneous_19265468
- Format
- –
- Schlagworte
- Amino Acid Substitution, Animals, Bacteriology, Biological and medical sciences, Cell Division - drug effects, Cells, Cultured, enterotoxin B, Enterotoxins - chemistry, Enterotoxins - genetics, Enterotoxins - metabolism, Enterotoxins - pharmacology, Enterotoxins - toxicity, Escherichia coli - genetics, Female, Fundamental and applied biological sciences. Psychology, Histidine - metabolism, HLA-DR4 Antigen - metabolism, Humans, Major histocompatibility complex II binding, Mice, Mice, Inbred C3H, Microbiology, Mitogenicity, Mitogens - genetics, Mitogens - pharmacology, Mutagenesis, Site-Directed, Mutation, Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains, Point Mutation, Recombinant Proteins - metabolism, Recombinant Proteins - pharmacology, Recombinant Proteins - toxicity, Spleen - cytology, Spleen - drug effects, Staphylococcal enterotoxin B, Staphylococcus aureus - genetics, T-Lymphocytes - drug effects, Toxicity, Tumor Cells, Cultured, Tyrosine - metabolism