Open Access
Nucleic Acids Research, volume 44, issue 18, pages 8897-8907
Antibiotic resistance evolved via inactivation of a ribosomal RNA methylating enzyme
1
Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158, USA.
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3
Department of Pharmaceutical Chemistry, University of California San Francisco, 600 16th St, MC2280 San Francisco, CA 94158, USA
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Publication type: Journal Article
Publication date: 2016-08-05
Journal:
Nucleic Acids Research
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 14.9
ISSN: 03051048, 13624962
PubMed ID:
27496281
Genetics
Abstract
Modifications of the bacterial ribosome regulate the function of the ribosome and modulate its susceptibility to antibiotics. By modifying a highly conserved adenosine A2503 in 23S rRNA, methylating enzyme Cfr confers resistance to a range of ribosome-targeting antibiotics. The same adenosine is also methylated by RlmN, an enzyme widely distributed among bacteria. While RlmN modifies C2, Cfr modifies the C8 position of A2503. Shared nucleotide substrate and phylogenetic relationship between RlmN and Cfr prompted us to investigate evolutionary origin of antibiotic resistance in this enzyme family. Using directed evolution of RlmN under antibiotic selection, we obtained RlmN variants that mediate low-level resistance. Surprisingly, these variants confer resistance not through the Cfr-like C8 methylation, but via inhibition of the endogenous RlmN C2 methylation of A2503. Detection of RlmN inactivating mutations in clinical resistance isolates suggests that the mechanism used by the in vitro evolved variants is also relevant in a clinical setting. Additionally, as indicated by a phylogenetic analysis, it appears that Cfr did not diverge from the RlmN family but from another distinct family of predicted radical SAM methylating enzymes whose function remains unknown.
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Citations by publishers
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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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Stojković V. et al. Antibiotic resistance evolved via inactivation of a ribosomal RNA methylating enzyme // Nucleic Acids Research. 2016. Vol. 44. No. 18. pp. 8897-8907.
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Stojković V., Noda Garcia L., Tawfik D. S., Galonić Fujimori D. Antibiotic resistance evolved via inactivation of a ribosomal RNA methylating enzyme // Nucleic Acids Research. 2016. Vol. 44. No. 18. pp. 8897-8907.
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TY - JOUR
DO - 10.1093/nar/gkw699
UR - https://doi.org/10.1093%2Fnar%2Fgkw699
TI - Antibiotic resistance evolved via inactivation of a ribosomal RNA methylating enzyme
T2 - Nucleic Acids Research
AU - Stojković, Vanja
AU - Noda Garcia, Lianet
AU - Tawfik, Dan S.
AU - Galonić Fujimori, Danica
PY - 2016
DA - 2016/08/05 00:00:00
PB - Oxford University Press
SP - 8897-8907
IS - 18
VL - 44
PMID - 27496281
SN - 0305-1048
SN - 1362-4962
ER -
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@article{2016_Stojković,
author = {Vanja Stojković and Lianet Noda Garcia and Dan S. Tawfik and Danica Galonić Fujimori},
title = {Antibiotic resistance evolved via inactivation of a ribosomal RNA methylating enzyme},
journal = {Nucleic Acids Research},
year = {2016},
volume = {44},
publisher = {Oxford University Press},
month = {aug},
url = {https://doi.org/10.1093%2Fnar%2Fgkw699},
number = {18},
pages = {8897--8907},
doi = {10.1093/nar/gkw699}
}
Cite this
MLA
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Stojković, Vanja, et al. “Antibiotic resistance evolved via inactivation of a ribosomal RNA methylating enzyme.” Nucleic Acids Research, vol. 44, no. 18, Aug. 2016, pp. 8897-8907. https://doi.org/10.1093%2Fnar%2Fgkw699.