ArticleRNA (New York, N.Y.)2011
Intrinsic resistance to aminoglycosides in Enterococcus faecium is conferred by the 16S rRNA m5C1404-specific methyltransferase EfmM.
Article in RNA (New York, N.Y.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 49 citations in OpenAlex.
- Compendium of RNA modifications for bacterial stress adaptation.Microbiology and molecular biology reviews : MMBR · 2026Review
- Clade-specific evolution and genome plasticity underlying antimicrobial resistance in Enterococcus faecium.Archives of microbiology · 2026Review
- Review
- Looking for ESKAPE Bacteria: Occurrence and Phenotypic Antimicrobial Resistance Profiles in Wild Birds from Northern and Central Italy Sites.Antibiotics (Basel, Switzerland) · 2025Article
- Crystal structure and biophysical characterisation of the enterococcal foldase PpiC, a cross-opsonic antigen against gram-positive nosocomial pathogens.The FEBS journal · 2025Article
- Resistance to last-resort antibiotics in enterococci.FEMS microbiology reviews · 2025Review
- Non-Clinical microbiology reviews · 2024Review
- The role of RNA modification in urological cancers: mechanisms and clinical potential.Discover oncology · 2023Review
- Vancomycin Resistance inMicroorganisms · 2022Review
- Review
- Advances in mRNA 5-methylcytosine modifications: Detection, effectors, biological functions, and clinical relevance.Molecular therapy. Nucleic acids · 2021Review
- Competent but complex communication: The phenomena of pheromone-responsive plasmids.PLoS pathogens · 2020Review
- Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation.EcoSal Plus · 2018Review
- Comparative genome analysis reveals key genetic factors associated with probiotic property in Enterococcus faecium strains.BMC genomics · 2018Article
- Antimicrobial Resistance inMicrobiology spectrum · 2018Review
- Antibiotic Resistance Mechanisms in Bacteria: Relationships Between Resistance Determinants of Antibiotic Producers, Environmental Bacteria, and Clinical Pathogens.Frontiers in microbiology · 2018Review
- Multiple Ribosomal RNA Operons in Bacteria; Their Concerted Evolution and Potential Consequences on the Rate of Evolution of Their 16S rRNA.Frontiers in microbiology · 2018Article
- Biofilm Formation and Motility Are Promoted by Cj0588-Directed Methylation of rRNA inFrontiers in cellular and infection microbiology · 2017Article
- Global Emergence and Dissemination of Enterococci as Nosocomial Pathogens: Attack of the Clones?Frontiers in microbiology · 2016Review
- Mechanisms of antibiotic resistance in enterococci.Expert review of anti-infective therapy · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aminoglycosides are ribosome-targeting antibiotics and a major drug group of choice in the treatment of serious enterococcal infections. Here we show that aminoglycoside resistance in Enterococcus faecium strain CIP 54-32 is conferred by the chromosomal gene efmM, encoding the E. faecium methyltransferase, as well as by the previously characterized aac(6')-Ii that encodes a 6'-N-aminoglycoside acetyltransferase. Inactivation of efmM in E. faecium increases susceptibility to the aminoglycosides kanamycin and tobramycin, and, conversely, expression of a recombinant version of efmM in Escherichia coli confers resistance to these drugs. The EfmM protein shows significant sequence similarity to E. coli RsmF (previously called YebU), which is a 5-methylcytidine (m⁵C) methyltransferase modifying 16S rRNA nucleotide C1407. The target for EfmM is shown by mass spectrometry to be a neighboring 16S rRNA nucleotide at C1404. EfmM uses the methyl group donor S-adenosyl-L-methionine to catalyze formation of m⁵C1404 on the 30S ribosomal subunit, whereas naked 16S rRNA and the 70S ribosome are not substrates. Addition of the 5-methyl to C1404 sterically hinders aminoglycoside binding. Crystallographic structure determination of EfmM at 2.28 Å resolution reveals an N-terminal domain connected to a central methyltransferase domain that is linked by a flexible lysine-rich region to two C-terminal subdomains. Mutagenesis of the methyltransferase domain established that two cysteines at specific tertiary locations are required for catalysis. The tertiary structure of EfmM is highly similar to that of RsmF, consistent with m⁵C formation at adjacent sites on the 30S subunit, while distinctive structural features account for the enzymes' respective specificities for nucleotides C1404 and C1407.
Indexed as
Identifiers
What OpenQuestion holds
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.