Evidence map›Paper›PMID 27182700›Full record

ArticlePloS one2016

Rapid Acquisition of Linezolid Resistance in Methicillin-Resistant Staphylococcus aureus: Role of Hypermutation and Homologous Recombination.

Shigekazu Iguchi, Tomonori Mizutani, Keiichi Hiramatsu, Ken Kikuchi

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.3field-weighted citation impact, top 20% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 38 citations in OpenAlex.

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  9. Molecular Basis of Non-β-Lactam Antibiotics Resistance inAntibiotics (Basel, Switzerland) · 2022
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  10. A Structurally CharacterizedMicrobiology spectrum · 2022
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  13. Potentiation of β-Lactams against Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2022
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  14. Article
  15. Antimicrobial Resistance in ESKAPE Pathogens.Clinical microbiology reviews · 2020
    Review
  16. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Shigekazu IguchiDepartment of Infection Control Science, Faculty of Medicine, Juntendo University, Tokyo, Japan.
Tomonori MizutaniDepartment of Infection Control Science, Faculty of Medicine, Juntendo University, Tokyo, Japan.
Keiichi HiramatsuDepartment of Infection Control Science, Faculty of Medicine, Juntendo University, Tokyo, Japan.
Ken KikuchiDepartment of Infection Control Science, Faculty of Medicine, Juntendo University, Tokyo, Japan.
Juntendo University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Drug Resistance, BacterialHomologous RecombinationMutationAnti-Bacterial AgentsDNA, Ribosomal SpacerGenome, BacterialGenomicsHumansLinezolidMethicillin-Resistant Staphylococcus aureusMicrobial Sensitivity TestsMutation RatePhylogenyPolymorphism, Single NucleotideRNA, RibosomalStaphylococcal InfectionsAnti-Bacterial AgentsDNA, Ribosomal SpacerLinezolidRNA, Ribosomal

Identifiers

PMID27182700
PMCPMC4868352
OpenAlexW2398091648

What OpenQuestion holds

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Registered trials

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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.