Mycobacterial mistranslation is necessary and sufficient for rifampicin phenotypic resistance
| Autor: | Babak Javid, Flavia Sorrentino, Padraig Deighan, Melody Toosky, Miaomiao Pan, Eric J. Rubin, Nina Jain, Wen Zheng, Jessica T. Pinkham |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Proteomics
Glutamine Molecular Sequence Data Mycobacterium smegmatis Glutamic Acid medicine.disease_cause Microbiology chemistry.chemical_compound RNA polymerase Drug Resistance Bacterial Protein biosynthesis medicine Amino Acid Sequence Asparagine Antibiotics Antitubercular Recombination Genetic Genetics Aspartic Acid Mutation Multidisciplinary biology DNA-Directed RNA Polymerases Biological Sciences biology.organism_classification Phenotype chemistry Protein Biosynthesis Rifampin Rifampicin medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 111:1132-1137 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1317580111 |
| Popis: | Errors are inherent in all biological systems. Errors in protein translation are particularly frequent giving rise to a collection of protein quasi-species, the diversity of which will vary according to the error rate. As mistranslation rates rise, these new proteins could produce new phenotypes, although none have been identified to date. Here, we find that mycobacteria substitute glutamate for glutamine and aspartate for asparagine at high rates under specific growth conditions. Increasing the substitution rate results in remarkable phenotypic resistance to rifampicin, whereas decreasing mistranslation produces increased susceptibility to the antibiotic. These phenotypic changes are reflected in differential susceptibility of RNA polymerase to the drug. We propose that altering translational fidelity represents a unique form of environmental adaptation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|