Evidence map›Paper›PMID 22664970›Full record

ArticleAntimicrobial agents and chemotherapy2012

Correlation between mutations in liaFSR of Enterococcus faecium and MIC of daptomycin: revisiting daptomycin breakpoints.

Jose M Munita, Diana Panesso, Lorena Diaz, Truc T Tran, Jinnethe Reyes, Audrey Wanger, Barbara E Murray, Cesar A Arias

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 1 pooled it
5.5field-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

71 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Evolution under vancomycin selection drives divergent collateral sensitivity patterns inProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Vancomycin Resistance inMicroorganisms · 2022
    Review
  13. Article
  14. Antimicrobial Susceptibility Testing for Enterococci.Journal of clinical microbiology · 2022
    Review
  15. Article
  16. Acquisition of Daptomycin Resistance byFrontiers in microbiology · 2022
    Article
  17. Article
  18. Daptomycin Resistance Occurs Predominantly inFrontiers in microbiology · 2021
    Article
  19. Resistance in Vancomycin-Resistant Enterococci.Infectious disease clinics of North America · 2020
    Review
  20. Two Cases of Vancomycin-ResistantOpen forum infectious diseases · 2020
    Article

11 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

8 authors at 3 institutions in 3 countries.

Jose M MunitaLaboratory for Antimicrobial Research, University of Texas Medical School at Houston, Houston, Texas, USA.
Diana Panesso
Lorena Diaz
Truc T Tran
Jinnethe Reyes
Audrey Wanger
Barbara E Murray
Cesar A Arias
The University of Texas Health Science Center at Houston · USThe University of Texas at Austin · USTexas Center for Infectious Disease · US

Funding

Molecular Mechanisms Of Daptomycin Resistance In EnterococciR01AI093749 · NIAID · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ARIAS, CESAR AUGUSTO · 2011 to 2015
$1.9M
Enterococcus faecium virulence: A molecular and therapeutic approachR00AI072961 · NIAID · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ARIAS, CESAR AUGUSTO · 2009 to 2010
$593k
Enterococcus faecium virulence: A molecular and therapeutic approachK99AI072961 · NIAID · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ARIAS, CESAR AUGUSTO · 2008 to 2008
$91k
NIAID NIH HHS K99 AI072961NIAID NIH HHS R00 AI072961NIAID NIH HHS R00 AI72961NIAID NIH HHS R01 AI093749NIAID NIH HHS R01 AI72961
6 · The paper itself

Abstract

Mutations in liaFSR, a three-component regulatory system controlling cell-envelope stress response, were recently linked with the emergence of daptomycin (DAP) resistance in enterococci. Our previous work showed that a liaF mutation increased the DAP MIC of a vancomycin-resistant Enterococcus faecalis strain from 1 to 3 μg/ml (the DAP breakpoint is 4 μg/ml), suggesting that mutations in the liaFSR system could be a pivotal initial event in the development of DAP resistance. With the hypothesis that clinical enterococcal isolates with DAP MICs between 3 and 4 μg/ml might harbor mutations in liaFSR, we studied 38 Enterococcus faecium bloodstream isolates, of which 8 had DAP MICs between 3 and 4 μg/ml by Etest in Mueller-Hinton agar. Interestingly, 6 of these 8 isolates had predicted amino acid changes in the LiaFSR system. Moreover, we previously showed that among 6 DAP-resistant E. faecium isolates (MICs of >4 μg/ml), 5 had mutations in liaFSR. In contrast, none of 16 E. faecium isolates with a DAP MIC of ≤2 μg/ml harbored mutations in this system (P < 0.0001). All but one isolate with liaFSR changes exhibited DAP MICs of ≥16 μg/ml by Etest using brain heart infusion agar (BHIA), a medium that better supports enterococcal growth. Our findings provide a strong association between DAP MICs within the upper susceptibility range and mutations in the liaFSR system. Concomitant susceptibility testing on BHIA may be useful for identifying these E. faecium first-step mutants. Our results also suggest that the current DAP breakpoint for E. faecium may need to be reevaluated.

Indexed as

Anti-Bacterial AgentsBacterial ProteinsBase SequenceCell WallDaptomycinDNA, BacterialDrug Resistance, BacterialEnterococcus faeciumMicrobial Sensitivity TestsMutationSequence Analysis, DNAVancomycinVancomycin ResistanceAnti-Bacterial AgentsBacterial ProteinsDaptomycinDNA, BacterialVancomycin

Identifiers

PMID22664970
PMCPMC3421602
OpenAlexW2107978429

What OpenQuestion holds

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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.