Mycobacterial mistranslation is necessary and sufficient for rifampicin phenotypic resistance
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Author
Javid, Babak
Sorrentino, Flavia
Toosky, Melody
Zheng, Wen
Pinkham, Jessica T.
Jain, Nina
Pan, Miaomiao
Deighan, Padraig
Rubin, Eric J.
Published Version
https://doi.org/10.1073/pnas.1317580111Metadata
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Javid, B., F. Sorrentino, M. Toosky, W. Zheng, J. T. Pinkham, N. Jain, M. Pan, P. Deighan, and E. J. Rubin. 2014. “Mycobacterial Mistranslation Is Necessary and Sufficient for Rifampicin Phenotypic Resistance.” Proceedings of the National Academy of Sciences 111 (3): 1132–37. https://doi.org/10.1073/pnas.1317580111.Abstract
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.Terms of Use
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