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Mycobacterial mistranslation is necessary and sufficient for rifampicin phenotypic resistance.

Authors
  • Javid, Babak
  • Sorrentino, Flavia
  • Toosky, Melody
  • Zheng, Wen
  • Pinkham, Jessica T
  • Jain, Nina
  • Pan, Miaomiao
  • Deighan, Padraig
  • Rubin, Eric J
Type
Published Article
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Publication Date
Jan 21, 2014
Volume
111
Issue
3
Pages
1132–1137
Identifiers
DOI: 10.1073/pnas.1317580111
PMID: 24395793
Source
Medline
Keywords
License
Unknown

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.

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