ArticlePloS one2016
Rapid Acquisition of Linezolid Resistance in Methicillin-Resistant Staphylococcus aureus: Role of Hypermutation and Homologous Recombination.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 38 citations in OpenAlex.
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- Surveillance of Antimicrobial Resistance and Multidrug Resistance Prevalence of Clinical Isolates in a Regional Hospital in Northern Greece.Antibiotics (Basel, Switzerland) · 2023Article
- Phenotypic and genotypic characterization of linezolid resistance and the effect of antibiotic combinations on methicillin-resistant Staphylococcus aureus clinical isolates.Annals of clinical microbiology and antimicrobials · 2023Article
- Antimicrobial resistance in methicillin-resistant staphylococcus aureus.Saudi journal of biological sciences · 2023Review
- Identification and Validation of a Novel Antibacterial Compound MZ-01 against Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2022Article
- Molecular Basis of Non-β-Lactam Antibiotics Resistance inAntibiotics (Basel, Switzerland) · 2022Review
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- Structural and functional characterization of fosfomycin resistance conferred by FosB from Enterococcus faecium.Protein science : a publication of the Protein Society · 2022Article
- Potentiation of β-Lactams against Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2022Article
- Characterization of compound A, a novel lincomycin derivative active against methicillin-resistant Staphylococcus aureus.The Journal of antibiotics · 2021Article
- Antimicrobial Resistance in ESKAPE Pathogens.Clinical microbiology reviews · 2020Review
- Emergence and Within-Host Genetic Evolution of Methicillin-ResistantAntimicrobial agents and chemotherapy · 2018Article
- Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe previously reported the case of a 64-year-old man with mediastinitis caused by Staphylococcus aureus in which the infecting bacterium acquired linezolid resistance after only 14 days treatment with linezolid. We therefore investigated relevant clinical isolates for possible mechanisms of this rapid acquisition of linezolid resistance.
methodsUsing clinical S. aureus isolates, we assessed the in vitro mutation rate and performed stepwise selection for linezolid resistance. To investigate homologous recombination, sequences were determined for each of the 23S ribosomal RNA (23S rRNA) loci; analyzed sequences spanned the entirety of each 23S rRNA gene, including domain V, as well as the 16S-23S intergenic spacer regions. We additionally performed next-generation sequencing on clinical strains to identify single-nucleotide polymorphisms compared to the N315 genome.
resultsStrains isolated from the patient prior to linezolid exposure (M5-M7) showed higher-level linezolid resistance than N315, and the pre-exposure strain (M2) exhibited more rapid acquisition of linezolid resistance than did N315. However, the mutation rates of these and contemporaneous clinical isolates were similar to those of N315, and the isolates did not exhibit any mutations in hypermutation-related genes. Sequences of the 23S rRNA genes and 16S-23S intergenic spacer regions were identical among the pre- and post-exposure clinical strains. Notably, all of the pre-exposure isolates harbored a recQ missense mutation (Glu69Asp) with respect to N315; such a lesion may have affected short sequence recombination (facilitating, for example, recombination among rrn loci). We hypothesize that this mechanism contributed to rapid acquisition of linezolid resistance.
conclusionsHypermutation and homologous recombination of the ribosomal RNA genes, including 23S rRNA genes, appear not to have been sources of the accelerated acquisition of linezolid resistance observed in our clinical case. Increased frequency of short sequence recombination may have resulted from a recQ variant in the infecting organism.
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