RNA, volume 22, issue 12, pages 1836-1843
Nonmutational compensation of the fitness cost of antibiotic resistance in mycobacteria by overexpression of tlyA rRNA methylase
Publication type: Journal Article
Publication date: 2016-10-03
PubMed ID:
27698071
Molecular Biology
Abstract
Several studies over the last few decades have shown that antibiotic resistance mechanisms frequently confer a fitness cost and that these costs can be genetically ameliorated by intra- or extragenic second-site mutations, often without loss of resistance. Another, much less studied potential mechanism by which the fitness cost of antibiotic resistance could be reduced is via a regulatory response where the deleterious effect of the resistance mechanism is lowered by a physiological alteration that buffers the mutational effect. In mycobacteria, resistance to the clinically used tuberactinomycin antibiotic capreomycin involves loss-of-function mutations in rRNA methylase TlyA or point mutations in 16S rRNA (in particular the A1408G mutation). Both of these alterations result in resistance by reducing drug binding to the ribosome. Here we show that alterations of tlyA gene expression affect both antibiotic drug susceptibility and fitness cost of drug resistance. In particular, we demonstrate that the common resistance mutation A1408G is accompanied by a physiological change that involves increased expression of the tlyA gene. This gene encodes an enzyme that methylates neighboring 16S rRNA position C1409, and as a result of increased TlyA expression the fitness cost of the A1408G mutation is significantly reduced. Our findings suggest that in mycobacteria, a nonmutational mechanism (i.e., gene regulatory) can restore fitness to genetically resistant bacteria. Our results also point to a new and clinically relevant treatment strategy to combat evolution of resistance in multidrug-resistant tuberculosis. Thus, by utilizing antagonistic antibiotic interactions, resistance evolution could be reduced.
Citations by journals
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PLoS ONE
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Tuberculosis
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1 publication, 2.63%
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1 publication, 2.63%
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1 publication, 2.63%
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The Lancet Infectious Diseases
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1 publication, 2.63%
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mSystems
1 publication, 2.63%
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1 publication, 2.63%
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1 publication, 2.63%
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1 publication, 2.63%
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1 publication, 2.63%
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1 publication, 2.63%
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1 publication, 2.63%
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1 publication, 2.63%
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Proceedings of the National Academy of Sciences of the United States of America
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Proceedings of the National Academy of Sciences of the United States of America
1 publication, 2.63%
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Russian Journal of Infection and Immunity
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Russian Journal of Infection and Immunity, 1, 2.63%
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1 publication, 2.63%
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Microbial Biotechnology
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1 publication, 2.63%
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Nature
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Nature
1 publication, 2.63%
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Citations by publishers
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Elsevier
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6 publications, 15.79%
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Frontiers Media S.A.
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Frontiers Media S.A.
5 publications, 13.16%
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American Society for Microbiology
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5 publications, 13.16%
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Springer Nature
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Springer Nature
4 publications, 10.53%
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Oxford University Press
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Oxford University Press
2 publications, 5.26%
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Multidisciplinary Digital Publishing Institute (MDPI)
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Multidisciplinary Digital Publishing Institute (MDPI)
2 publications, 5.26%
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Public Library of Science (PLoS)
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2 publications, 5.26%
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Pleiades Publishing
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1 publication, 2.63%
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Mary Ann Liebert
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Mary Ann Liebert
1 publication, 2.63%
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The Royal Society
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The Royal Society
1 publication, 2.63%
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Hindawi Limited
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Hindawi Limited
1 publication, 2.63%
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Proceedings of the National Academy of Sciences (PNAS)
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Proceedings of the National Academy of Sciences (PNAS)
1 publication, 2.63%
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Saint Petersburg Pasteur Institute
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Saint Petersburg Pasteur Institute, 1, 2.63%
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1 publication, 2.63%
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Wiley
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Wiley
1 publication, 2.63%
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Freihofer P. et al. Nonmutational compensation of the fitness cost of antibiotic resistance in mycobacteria by overexpression of tlyA rRNA methylase // RNA. 2016. Vol. 22. No. 12. pp. 1836-1843.
GOST all authors (up to 50)
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Freihofer P., Akbergenov R., Teo Y., Juskeviciene R., Andersson D., Böttger E. C. Nonmutational compensation of the fitness cost of antibiotic resistance in mycobacteria by overexpression of tlyA rRNA methylase // RNA. 2016. Vol. 22. No. 12. pp. 1836-1843.
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TY - JOUR
DO - 10.1261/rna.057257.116
UR - https://doi.org/10.1261%2Frna.057257.116
TI - Nonmutational compensation of the fitness cost of antibiotic resistance in mycobacteria by overexpression of tlyA rRNA methylase
T2 - RNA
AU - Freihofer, Pietro
AU - Akbergenov, Rashid
AU - Teo, Youjin
AU - Juskeviciene, Reda
AU - Andersson, Dan
AU - Böttger, Erik C.
PY - 2016
DA - 2016/10/03 00:00:00
PB - Cold Spring Harbor Laboratory
SP - 1836-1843
IS - 12
VL - 22
PMID - 27698071
SN - 1355-8382
SN - 1469-9001
ER -
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@article{2016_Freihofer,
author = {Pietro Freihofer and Rashid Akbergenov and Youjin Teo and Reda Juskeviciene and Dan Andersson and Erik C. Böttger},
title = {Nonmutational compensation of the fitness cost of antibiotic resistance in mycobacteria by overexpression of tlyA rRNA methylase},
journal = {RNA},
year = {2016},
volume = {22},
publisher = {Cold Spring Harbor Laboratory},
month = {oct},
url = {https://doi.org/10.1261%2Frna.057257.116},
number = {12},
pages = {1836--1843},
doi = {10.1261/rna.057257.116}
}
Cite this
MLA
Copy
Freihofer, Pietro, et al. “Nonmutational compensation of the fitness cost of antibiotic resistance in mycobacteria by overexpression of tlyA rRNA methylase.” RNA, vol. 22, no. 12, Oct. 2016, pp. 1836-1843. https://doi.org/10.1261%2Frna.057257.116.