ArticleAntimicrobial agents and chemotherapy2012
Fitness cost and interference of Arm/Rmt aminoglycoside resistance with the RsmF housekeeping methyltransferases.
Article in Antimicrobial agents and chemotherapy, 2012. 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, 43 citations in OpenAlex.
- Mechanism of 30S subunit recognition and modification by the conserved bacterial ribosomal RNA methyltransferase RsmI.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Biological cost of aminoglycoside resistance Arm/Kam 16S rRNA methyltransferases from natural antibiotic producers and clinical pathogens.Antimicrobial agents and chemotherapy · 2025Article
- Discovery of First-in-Class Inhibitors Targeting a Pathogen-Associated Aminoglycoside-Resistance 16S rRNA Methyltransferase.ACS infectious diseases · 2025Article
- c-di-GMP inhibits rRNA methylation and impairs ribosome assembly in the presence of kanamycin.EMBO reports · 2025Article
- Bacteria can compensate the fitness costs of amplified resistance genes via a bypass mechanism.Nature communications · 2024Article
- 30S subunit recognition and G1405 modification by the aminoglycoside-resistance 16S ribosomal RNA methyltransferase RmtC.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- 30S subunit recognition and G1405 modification by the aminoglycoside-resistance 16S ribosomal RNA methyltransferase RmtC.bioRxiv : the preprint server for biology · 2023Article
- Ribosome-targeting antibiotics and resistanceRSC medicinal chemistry · 2023Review
- Public health implications of plasmid-mediated quinolone and aminoglycoside resistance genes inEpidemiology and infection · 2022Article
- Molecular Characterization of WCK 5222 (Cefepime/Zidebactam)-Resistant Mutants Developed from a Carbapenem-Resistant Pseudomonas aeruginosa Clinical Isolate.Microbiology spectrum · 2022Article
- Conjugation of a Hybrid Plasmid Encoding Hypervirulence and Carbapenem Resistance inFrontiers in microbiology · 2022Article
- Nonessential tRNA and rRNA modifications impact the bacterial response to sub-MIC antibiotic stress.microLife · 2022Article
- Aminoglycoside Resistance: Updates with a Focus on Acquired 16S Ribosomal RNA Methyltransferases.Infectious disease clinics of North America · 2020Review
- Extensive antimicrobial resistance mobilization via multicopy plasmid encapsidation mediated by temperate phages.The Journal of antimicrobial chemotherapy · 2020Article
- Broad-spectrum suppression of bacterial pneumonia by aminoglycoside-propagated Acinetobacter baumannii.PLoS pathogens · 2020Article
- Comprehensive Functional Analysis ofFrontiers in genetics · 2020Article
- Evolution of Antibiotic Resistance in Surrogates ofFrontiers in microbiology · 2020Article
- Molecular Characterization of Carbapenem-Resistant Acinetobacter baumannii in the Intensive Care Unit of Uruguay's University Hospital Identifies the First rmtC Gene in the Species.Microbial drug resistance (Larchmont, N.Y.) · 2018Article
- Antimicrobial Resistance inMicrobiology spectrum · 2018Review
- Spread of mcr-1-carrying Enterobacteriaceae in sewage water from Spain.The Journal of antimicrobial chemotherapy · 2017Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Arm/Rmt methyltransferases have emerged recently in pathogenic bacteria as enzymes that confer high-level resistance to 4,6-disubstituted aminoglycosides through methylation of the G1405 residue in the 16S rRNA (like ArmA and RmtA to -E). In prokaryotes, nucleotide methylations are the most common type of rRNA modification, and they are introduced posttranscriptionally by a variety of site-specific housekeeping enzymes to optimize ribosomal function. Here we show that while the aminoglycoside resistance methyltransferase RmtC methylates G1405, it impedes methylation of the housekeeping methyltransferase RsmF at position C1407, a nucleotide that, like G1405, forms part of the aminoglycoside binding pocket of the 16S rRNA. To understand the origin and consequences of this phenomenon, we constructed a series of in-frame knockout and knock-in mutants of Escherichia coli, corresponding to the genotypes rsmF(+), ΔrsmF, rsmF(+) rmtC(+), and ΔrsmF rmtC(+). When analyzed for the antimicrobial resistance pattern, the ΔrsmF bacteria had a decreased susceptibility to aminoglycosides, including 4,6- and 4,5-deoxystreptamine aminoglycosides, showing that the housekeeping methylation at C1407 is involved in intrinsic aminoglycoside susceptibility in E. coli. Competition experiments between the isogenic E. coli strains showed that, contrary to expectation, acquisition of rmtC does not entail a fitness cost for the bacterium. Finally, matrix-assisted laser desorption ionization (MALDI) mass spectrometry allowed us to determine that RmtC methylates the G1405 residue not only in presence but also in the absence of aminoglycoside antibiotics. Thus, the coupling between housekeeping and acquired methyltransferases subverts the methylation architecture of the 16S rRNA but elicits Arm/Rmt methyltransferases to be selected and retained, posing an important threat to the usefulness of aminoglycosides worldwide.
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