ArticleAntimicrobial agents and chemotherapy2009
Novel ribosomal mutations in Staphylococcus aureus strains identified through selection with the oxazolidinones linezolid and torezolid (TR-700).
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 202 citations in OpenAlex.
- Analysis of the phase 3 ESTABLISH trials of tedizolid versus linezolid in acute bacterial skin and skin structure infections.Antimicrobial agents and chemotherapy · 2015Trial
- Pharmacokinetics of tedizolid following oral administration: single and multiple dose, effect of food, and comparison of two solid forms of the prodrug.Pharmacotherapy · 2014Trial
- Unlocking the Bioactive Potential of Streptomyces: A Multidisciplinary Approach to Strain Improvement.MicrobiologyOpen · 2026Review
- Article
- Identification of genetic mutations conferring tedizolid resistance in MRSA mutants.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025Article
- Characterisation ofJAC-antimicrobial resistance · 2025Article
- Resistance mechanisms and tedizolid susceptibility in clinical isolates of linezolid-resistant bacteria in Japan.JAC-antimicrobial resistance · 2025Article
- Resistance to last-resort antibiotics in enterococci.FEMS microbiology reviews · 2025Review
- Resistance to linezolid in Staphylococcus aureus by mutation, modification, and acquisition of genes.The Journal of antibiotics · 2025Review
- Diversity in Adaptive Evolution of Methicillin-ResistantInfection and drug resistance · 2025Article
- Differences in oxazolidinone resistance mechanisms and small colony variants emergence ofEmerging microbes & infections · 2024Article
- Parallel evolution of linezolid-resistantMicrobiology spectrum · 2023Article
- Staph wars: the antibiotic pipeline strikes back.Microbiology (Reading, England) · 2023Review
- Parallel Evolution of Linezolid ResistantbioRxiv : the preprint server for biology · 2023Article
- Co-Existence of Oxazolidinone Resistance GenesAntibiotics (Basel, Switzerland) · 2023Article
- Antimicrobial resistance in methicillin-resistant staphylococcus aureus.Saudi journal of biological sciences · 2023Review
- Vancomycin Resistance inMicroorganisms · 2022Review
- Molecular Basis of Non-β-Lactam Antibiotics Resistance inAntibiotics (Basel, Switzerland) · 2022Review
- A Structurally CharacterizedMicrobiology spectrum · 2022Article
- Mechanisms of linezolid resistance in Staphylococcus capitis with the novel mutation C2128T in the 23S rRNA gene in China.BMC microbiology · 2022Article
36 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TR-700 (torezolid), the active moiety of the novel oxazolidinone phosphate prodrug TR-701, is highly potent against gram-positive pathogens, including strains resistant to linezolid (LZD). Here we investigated the potential of Staphylococcus aureus strains ATCC 29213 (methicillin-susceptible S. aureus [MSSA]) and ATCC 33591 (methicillin-resistant S. aureus [MRSA]) to develop resistance to TR-700. The spontaneous frequencies of mutation of MSSA 29213 and MRSA 33591 resulting in reduced susceptibility to TR-700 at 2 x the MIC were 1.1 x 10(-10) and 1.9 x 10(-10), respectively. These values are approximately 16-fold lower than the corresponding LZD spontaneous mutation frequencies of both strains. Following 30 serial passages in the presence of TR-700, the MIC for MSSA 29213 remained constant (0.5 microg/ml) while increasing eightfold (0.25 to 2.0 microg/ml) for MRSA 33591. Serial passage of MSSA 29213 and MRSA 33591 in LZD resulted in 64- and 32-fold increases in LZD resistance (2 to 128 microg/ml and 1 to 32 microg/ml, respectively). Domain V 23S rRNA gene mutations (Escherichia coli numbering) found in TR-700-selected mutants included T2500A and a novel coupled T2571C/G2576T mutation, while LZD-selected mutants included G2447T, T2500A, and G2576T. We also identified mutations correlating with decreased susceptibility to TR-700 and LZD in the rplC and rplD genes, encoding the 50S ribosomal proteins L3 and L4, respectively. L3 mutations included Gly152Asp, Gly155Arg, Gly155Arg/Met169Leu, and DeltaPhe127-His146. The only L4 mutation detected was Lys68Gln. TR-700 maintained a fourfold or greater potency advantage over LZD against all strains with ribosomal mutations. These data bring to light a variety of novel and less-characterized mutations associated with S. aureus resistance to oxazolidinones and demonstrate the low resistance potential of torezolid.
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