ArticleAntimicrobial agents and chemotherapy2013
The genetic environment of the cfr gene and the presence of other mechanisms account for the very high linezolid resistance of Staphylococcus epidermidis isolate 426-3147L.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- The Evolution of Symbiosis inBiomolecules · 2026Review
- Review
- Whole-Genome Sequencing of Linezolid-Resistant and Linezolid-Intermediate-SusceptibilityMicroorganisms · 2025Article
- The pathogenicity and virulence of the opportunistic pathogenVirulence · 2024Review
- Clinical, Bacteriological, and Genetic Characterization of Bone and Joint Infections Involving Linezolid-Resistant Staphylococcus epidermidis: a Retrospective Multicenter Study in French Reference Centers.Microbiology spectrum · 2023Article
- Directed evolution of the rRNA methylating enzyme Cfr reveals molecular basis of antibiotic resistance.eLife · 2022Article
- Mobile Oxazolidinone Resistance Genes in Gram-Positive and Gram-Negative Bacteria.Clinical microbiology reviews · 2021Article
- Genomic and Phenotypic Analysis of Linezolid-ResistantMicroorganisms · 2021Article
- Prevalence and mechanisms of linezolid resistance among staphylococcal clinical isolates from Egypt.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2021Article
- Prevalence and molecular characterization of methicillin-resistant Staphylococcus aureus with mupirocin, fusidic acid and/or retapamulin resistance.BMC microbiology · 2020Article
- Analysis of combined resistance to oxazolidinones and phenicols among bacteria from dogs fed with raw meat/vegetables and the respective food items.Scientific reports · 2019Article
- Ribosome-Targeting Antibiotics: Modes of Action, Mechanisms of Resistance, and Implications for Drug Design.Annual review of biochemistry · 2018Review
- Lincosamides, Streptogramins, Phenicols, and Pleuromutilins: Mode of Action and Mechanisms of Resistance.Cold Spring Harbor perspectives in medicine · 2016Review
- Article
- Complete nucleotide sequence of cfr-carrying IncX4 plasmid pSD11 from Escherichia coli.Antimicrobial agents and chemotherapy · 2015Article
- Dissemination of the same cfr-carrying plasmid among methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococcal isolates in China.Antimicrobial agents and chemotherapy · 2015Article
- Mutations in the bacterial ribosomal protein l3 and their association with antibiotic resistance.Antimicrobial agents and chemotherapy · 2015Article
- tRNAs as antibiotic targets.International journal of molecular sciences · 2014Review
- Linezolid-resistant Staphylococcus aureus strain 1128105, the first known clinical isolate possessing the cfr multidrug resistance gene.Antimicrobial agents and chemotherapy · 2014Article
- Ribosome-targeting antibiotics and mechanisms of bacterial resistance.Nature reviews. Microbiology · 2014Review
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The clinical Staphylococcus epidermidis isolate 426-3147L exhibits an unusually high resistance to linezolid that exceeds 256 μg/ml. The presence of the cfr gene, encoding the RNA methyltransferase targeting an rRNA nucleotide located in the linezolid binding site, accounts for a significant fraction of resistance. The association of cfr with a multicopy plasmid is one of the factors that contribute to its elevated expression. Mapping of the cfr transcription start sites identified the native cfr promoter. Furthermore, analysis of the cfr transcripts in Staphylococcus epidermidis 426-3147L showed that some of them originate from the upstream plasmid-derived promoters whose activity contributes to efficient cfr transcription. The genetic environment of the cfr gene and its idiosyncratic transcription pattern result in increased activity of Cfr methyltransferase, leading to a high fraction of the ribosomes being methylated at A2503 of the 23S rRNA. Curing of the Staphylococcus epidermidis 426-3147L isolate from the cfr-containing plasmid reduced the linezolid MIC to 64 μg/ml, indicating that other determinants contribute to resistance. Nucleotide sequence analysis revealed the presence of the C2534T mutation in two of the six 23S rRNA gene alleles as well as the presence of mutations in the genes of ribosomal proteins L3 and L4, which were previously implicated in linezolid resistance. Thus, the combination of resistance mechanisms operating through alteration of the drug target site appears to cause an unusually high level of linezolid resistance in the isolate.
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