Evidence map›Paper›PMID 22238576›Full record

ArticlePloS one2012

Whole genome characterization of the mechanisms of daptomycin resistance in clinical and laboratory derived isolates of Staphylococcus aureus.

Anton Y Peleg, Spiros Miyakis, Doyle V Ward, Ashlee M Earl, Aileen Rubio, David R Cameron, Satish Pillai, Robert C Moellering, George M Eliopoulos

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers.

0numbers the graph read from it
0cells of the map it votes in
137citing papers in PubMed
10.3field-weighted citation impact, top 1% 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

137 citing papers in PubMed, 242 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Characterisation ofJAC-antimicrobial resistance · 2025
    Article
  11. Article
  12. DefectivemSphere · 2024
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Identification ofJournal of bacteriology · 2024
    Article
  18. Genomic Insights intoPathogens (Basel, Switzerland) · 2024
    Article
  19. Article
  20. Phenotypic and genetic characterization of daptomycin non-susceptibleFrontiers in cellular and infection microbiology · 2024
    Article

77 more citing papers are in PubMed but not listed here.

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

9 authors at 5 institutions in 3 countries.

Anton Y PelegDepartment of Microbiology, School of Biomedical Sciences, Monash University, Melbourne, Australia. apeleg@bidmc.harvard.edu
Spiros Miyakis
Doyle V Ward
Ashlee M Earl
Aileen Rubio
David R Cameron
Satish Pillai
Robert C Moellering
George M Eliopoulos
Beth Israel Deaconess Medical Center · USBroad Institute · USHarvard University · USCubist Pharmaceuticals (United States) · USMonash University · AU

Funding

NIAID NIH HHS HHSN266200400001CNIAID NIH HHS HHSN272200900018C
6 · The paper itself

Abstract

backgroundDaptomycin remains one of our last-line anti-staphylococcal agents. This study aims to characterize the genetic evolution to daptomycin resistance in S. aureus.

methodsWhole genome sequencing was performed on a unique collection of isogenic, clinical (21 strains) and laboratory (12 strains) derived strains that had been exposed to daptomycin and developed daptomycin-nonsusceptibility. Electron microscopy (EM) and lipid membrane studies were performed on selected isolates.

resultsOn average, six coding region mutations were observed across the genome in the clinical daptomycin exposed strains, whereas only two mutations on average were seen in the laboratory exposed pairs. All daptomycin-nonsusceptible strains had a mutation in a phospholipid biosynthesis gene. This included mutations in the previously described mprF gene, but also in other phospholipid biosynthesis genes, including cardiolipin synthase (cls2) and CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase (pgsA). EM and lipid membrane composition analyses on two clinical pairs showed that the daptomycin-nonsusceptible strains had a thicker cell wall and an increase in membrane lysyl-phosphatidylglycerol.

conclusionPoint mutations in genes coding for membrane phospholipids are associated with the development of reduced susceptibility to daptomycin in S. aureus. Mutations in cls2 and pgsA appear to be new genetic mechanisms affecting daptomycin susceptibility in S. aureus.

Indexed as

Anti-Bacterial AgentsCell WallDaptomycinDrug Resistance, BacterialGenome, BacterialHumansLaboratories, HospitalLipid MetabolismMicrobial Sensitivity TestsModels, BiologicalPatientsSequence Analysis, DNAStaphylococcal InfectionsStaphylococcus aureusAnti-Bacterial AgentsDaptomycin

Identifiers

PMID22238576
PMCPMC3253072
OpenAlexW2169200218

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.