ArticleMolecular microbiology2012
Capreomycin susceptibility is increased by TlyA-directed 2'-O-methylation on both ribosomal subunits.
Article in Molecular microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 48 citations in OpenAlex.
- Compendium of RNA modifications for bacterial stress adaptation.Microbiology and molecular biology reviews : MMBR · 2026Review
- Emergence, evolution, and global dissemination of antimicrobial resistance: A One Health review.Archives of microbiology · 2026Review
- TlyA is a 23S and 16S 2'-O-methylcytidine methyltransferase important for ribosome assembly in Bacillus subtilis.Nucleic acids research · 2026Article
- Distant ribose 2'-O-methylation of 23S rRNA helix 69 pre-orders the capreomycin drug binding pocket at the ribosome subunit interface.Nucleic acids research · 2025Article
- Microevolutionary models and multi-omics analysis uncover the cross-drug resistance characteristics of capreomycin-selectedCurrent research in microbial sciences · 2025Article
- Increased Motility inInternational journal of molecular sciences · 2024Article
- TheRNA (New York, N.Y.) · 2024Article
- OvercomingACS omega · 2023Review
- Genome-wide association studies of global Mycobacterium tuberculosis resistance to 13 antimicrobials in 10,228 genomes identify new resistance mechanisms.PLoS biology · 2022Article
- 50S subunit recognition and modification by theProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Tuberactinomycin antibiotics: Biosynthesis, anti-mycobacterial action, and mechanisms of resistance.Frontiers in microbiology · 2022Review
- Article
- Virulence properties of Campylobacter jejuni are enhanced by displaying a mycobacterial TlyA methylation pattern in its rRNA.Cellular microbiology · 2020Article
- Article
- The Mechanisms of Action of Ribosome-Targeting Peptide Antibiotics.Frontiers in molecular biosciences · 2018Review
- Pseudouridine modifications influence binding of aminoglycosides to helix 69 of bacterial ribosomes.Organic & biomolecular chemistry · 2017Article
- A Novel Motif for S-Adenosyl-l-methionine Binding by the Ribosomal RNA Methyltransferase TlyA from Mycobacterium tuberculosis.The Journal of biological chemistry · 2017Article
- Biofilm Formation and Motility Are Promoted by Cj0588-Directed Methylation of rRNA inFrontiers in cellular and infection microbiology · 2017Article
- The Forgotten Virulence Factor: The 'non-conventional' Hemolysin TlyA And Its Role in Helicobacter pylori Infection.Current microbiology · 2016Review
- Nonmutational compensation of the fitness cost of antibiotic resistance in mycobacteria by overexpression of tlyA rRNA methylase.RNA (New York, N.Y.) · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The binding site of the cyclic peptide antibiotics capreomycin and viomycin is located on the ribosomal subunit interface close to nucleotides C1409 in 16S rRNA and C1920 in 23S rRNA. In Mycobacterium tuberculosis, the 2'-hydroxyls of both nucleotides are methylated by the enzyme TlyA. Loss of these methylations through inactivation of TlyA confers resistance to capreomycin and viomycin. We report here that TlyA orthologues occur in diverse bacteria and fall into two distinct groups. One group, now termed TlyA(I) , has shorter N- and C-termini and methylates only C1920; the second group (now TlyA(II) ) includes the mycobacterial enzyme, and these longer orthologues methylate at both C1409 and C1920. Ribosomal subunits are the preferred substrates for both groups of orthologues. Amino acid substitutions at the N-terminus of TlyA(II) reduce its ability to methylate these substrates. Growing pairs of recombinant TlyA(II) Escherichia coli strains in competition shows that even subtle changes in the level of rRNA methylation lead to significant differences in susceptibility to sub-inhibitory concentrations of capreomycin. The findings reveal that 2'-O-methyls at both C1409 and C1920 play a role in facilitating the inhibitory effects of capreomycin and viomycin on the bacterial ribosome.
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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.