Evidence map›Paper›PMID 25226591›Full record

ArticlePloS one2014

Phenotypic and genotypic characterization of daptomycin-resistant methicillin-resistant Staphylococcus aureus strains: relative roles of mprF and dlt operons.

Nagendra N Mishra, Arnold S Bayer, Christopher Weidenmaier, Timo Grau, Stefanie Wanner, Stefania Stefani, Viviana Cafiso, Taschia Bertuccio, Michael R Yeaman, Cynthia C Nast and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

72 citing papers in PubMed, 114 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Structural Insights into theBiomolecules · 2025
    Article
  7. Article
  8. Article
  9. Article
  10. The Complex Intracellular Lifecycle ofInternational journal of molecular sciences · 2024
    Review
  11. Review
  12. Phenotypic and genetic characterization of daptomycin non-susceptibleFrontiers in cellular and infection microbiology · 2024
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Molecular Basis of Non-β-Lactam Antibiotics Resistance inAntibiotics (Basel, Switzerland) · 2022
    Review
  18. Article
  19. Article
  20. Article

12 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

11 authors at 7 institutions in 3 countries.

Nagendra N MishraDivision of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States of America; The David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
Arnold S BayerDivision of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States of America; The David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
Christopher WeidenmaierInterfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany; German Center for Infection Research (DZIF), Tübingen, Germany.
Timo GrauInterfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
Stefanie WannerInterfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
Stefania StefaniDepartment of Biomedical Sciences-Microbiology, University of Catania, Catania, Italy.
Viviana CafisoDepartment of Biomedical Sciences-Microbiology, University of Catania, Catania, Italy.
Taschia BertuccioDepartment of Biomedical Sciences-Microbiology, University of Catania, Catania, Italy.
Michael R YeamanDivision of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States of America; The David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America; Division of Molecular Medicine, Harbor-UCLA Medical Center, Torrance, California, United States of America.
Cynthia C NastThe David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America; Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Soo-Jin YangDivision of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States of America; The David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
University of Catania · ITUCLA Medical Center · USUniversity of Tübingen · DEGerman Center for Infection Research · DEHarbor–UCLA Medical Center · USThe Lundquist Institute · USUniversity of California, Los Angeles · US

Funding

Staphylococcal Adaptations to Platelet Microbicidal ProteinR01AI039108 · NIAID · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · PI BAYER, ARNOLD S · 1997 to 2016
$5.1M
NIAID NIH HHS AI-111611NIAID NIH HHS AI-39108-15NIAID NIH HHS R01 AI039108
6 · The paper itself

Abstract

Development of in vivo daptomycin resistance (DAP-R) among Staphylococcus aureus clinical isolates, in association with clinical treatment failures, has become a major therapeutic problem. This issue is especially relevant to methicillin-resistant S. aureus (MRSA) strains in the context of invasive endovascular infections. In the current study, we used three well-characterized and clinically-derived DAP-susceptible (DAP-S) vs. resistant (DAP-R) MRSA strain-pairs to elucidate potential genotypic mechanisms of the DAP-R phenotype. In comparison to the DAP-S parental strains, DAP-R isolates demonstrated (i) altered expression of two key determinants of net positive surface charge, either during exponential or stationary growth phases (i.e., dysregulation of dltA and mprF), (ii) a significant increase in the D-alanylated wall teichoic acid (WTA) content in DAP-R strains, reflecting DltA gain-in-function; (iii) heightened elaboration of lysinylated-phosphatidylglyderol (L-PG) in DAP-R strains, reflecting MprF gain-in-function; (iv) increased cell membrane (CM) fluidity, and (v) significantly reduced susceptibility to prototypic cationic host defense peptides of platelet and leukocyte origins. In the tested DAP-R strains, genes conferring positive surface charge were dysregulated, and their functionality altered. However, there were no correlations between relative surface positive charge or cell wall thickness and the observed DAP-R phenotype. Thus, charge repulsion mechanisms via altered surface charge may not be sufficient to explain the DAP-R outcome. Instead, changes in the compositional or biophysical order of the DAP CM target of such DAP-R strains (i.e., increased fluidity) may be essential to this phenotype. Taken together, DAP-R in S. aureus appears to involve multi-factorial and strain-specific adaptive mechanisms.

Indexed as

Drug Resistance, BacterialGenotypeMicrobial Sensitivity TestsAnti-Bacterial AgentsAntimicrobial Cationic PeptidesCell WallDaptomycinFatty AcidsGene Expression Regulation, BacterialHumansMethicillin-Resistant Staphylococcus aureusOperonPhospholipidsTeichoic AcidsAnti-Bacterial AgentsAntimicrobial Cationic PeptidesDaptomycinFatty AcidsPhospholipidsTeichoic Acids

Identifiers

PMID25226591
PMCPMC4166420
OpenAlexW2046532579

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.