ArticleNucleic acids research2016
Antibiotic resistance evolved via inactivation of a ribosomal RNA methylating enzyme.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 50 citations in OpenAlex.
- Compendium of RNA modifications for bacterial stress adaptation.Microbiology and molecular biology reviews : MMBR · 2026Review
- A target-guided drug repurposing strategy for antibacterial discovery.BMC microbiology · 2026Article
- Structural Analysis of 23S rRNA Methylating Enzyme Cfr Reveals RNA-Binding Determinants for Methylation Regiospecificity and Antibiotic Resistance.ACS infectious diseases · 2026Article
- A Frameshift Mutation in the MethyltransferaseComputational and structural biotechnology journal · 2026Article
- Review
- Structural analysis of 23S rRNA methylating enzyme Cfr reveals RNA binding determinants for methylation regiospecificity and antibiotic resistance.bioRxiv : the preprint server for biology · 2025Article
- Bacterial ribosome heterogeneity facilitates rapid response to stress.Journal of bacteriology · 2025Review
- The structure of the human 80S ribosome at 1.9 Å resolution reveals the molecular role of chemical modifications and ions in RNA.Nature structural & molecular biology · 2024Article
- Epitranscriptional m6A modification of rRNA negatively impacts translation and host colonization in Staphylococcus aureus.PLoS pathogens · 2024Article
- The rate and role of pseudogenes of theMicrobial genomics · 2022Article
- Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria.Microorganisms · 2022Review
- Directed evolution of the rRNA methylating enzyme Cfr reveals molecular basis of antibiotic resistance.eLife · 2022Article
- Specialised ribosomes as versatile regulators of gene expression.RNA biology · 2022Review
- MALDI-TOF Mass Spectrometry Technology as a Tool for the Rapid Diagnosis of Antimicrobial Resistance in Bacteria.Antibiotics (Basel, Switzerland) · 2021Review
- Methylation of Ribosomal RNA: A Mitochondrial Perspective.Frontiers in genetics · 2020Review
- Article
- Analysis of RNA Methylation by Phylogenetically Diverse Cfr RadicalBiochemistry · 2019Article
- Unveiling the structural features that determine the dual methyltransferase activities of Streptococcus pneumoniae RlmCD.PLoS pathogens · 2018Article
- Review
- Epistatic control of intrinsic resistance by virulence genes in Listeria.PLoS genetics · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.