Evidence map›Paper›PMID 21968365›Full record

ArticleAntimicrobial agents and chemotherapy2011

Relationship of agr expression and function with virulence and vancomycin treatment outcomes in experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

Kati Seidl, Liang Chen, Arnold S Bayer, Wessam Abdel Hady, Barry N Kreiswirth, Yan Q Xiong

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

47 citing papers in PubMed, 62 citations in OpenAlex.

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  13. Vegetation Formation inFrontiers in cellular and infection microbiology · 2022
    Article
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  16. Vancomycin MIC and agr dysfunction in invasive MRSA infections in southern Brazil.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2020
    Article
  17. Antibiotic resistance and typing ofIranian journal of basic medical sciences · 2020
    Article
  18. Article
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  20. Science translational medicine · 2020
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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

6 authors at 3 institutions in 1 country.

Kati SeidlLos Angeles Biomedical Research Institute at Harbor—UCLA Medical Center, Torrance, California 90502, USA.
Liang Chen
Arnold S Bayer
Wessam Abdel Hady
Barry N Kreiswirth
Yan Q Xiong
The Lundquist Institute · USInternational Center for Public Health · USHarbor–UCLA Medical Center · 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 R01 AI039108
6 · The paper itself

Abstract

The accessory gene regulator (agr) locus has been shown to be important for virulence in several animal models of Staphylococcus aureus infection. However, the role of agr in human infections, and specifically in antibiotic treatment, is controversial. Interestingly, agr dysfunction has been associated with reduced vancomycin responses. To systematically investigate the role of agr in virulence and treatment outcome in the context of endovascular infection, 10 well-characterized vancomycin-susceptible methicillin-resistant S. aureus (MRSA) bloodstream isolates (5 agr-I [clonal complex 45, or CC45] and 5 agr-II [CC5]) were studied for (i) agr function, (ii) RNAIII transcriptional profiles, (iii) agr locus sequences, (iv) intrinsic virulence and responses to vancomycin therapy in an experimental infective endocarditis (IE) model, and (v) in vivo RNAIII expression. Significant differences in agr function (determined by delta-hemolysin activity) correlated with the time point of RNAIII transcription (earlier RNAIII onset equals increased agr function). Unexpectedly, four MRSA strains with strong delta-hemolysin activities exhibited significant resistance to vancomycin treatment in experimental IE. In contrast, five of six MRSA strains with weak or no delta-hemolysin activity were highly susceptible to vancomycin therapy in the IE model. agr sequence analyses showed no common single-nucleotide polymorphism predictive of agr functionality. In vivo RNAIII expression in cardiac vegetations did not correlate with virulence or vancomycin treatment outcomes in the IE model. Inactivation of agr in two strains with strong delta-hemolysin activity did not affect virulence or the in vivo efficacy of vancomycin. Our findings suggest that agr dysfunction does not correlate with vancomycin treatment failures in this experimental IE model in two distinct MRSA genetic backgrounds.

Indexed as

Gene Expression Regulation, BacterialAnimalsAnti-Bacterial AgentsBacterial ProteinsDisease Models, AnimalEndocarditis, BacterialGenes, RegulatorHumansMethicillin-Resistant Staphylococcus aureusMicrobial Sensitivity TestsRabbitsStaphylococcal InfectionsTrans-ActivatorsTreatment OutcomeVancomycinVirulenceAgr protein, Staphylococcus aureusAnti-Bacterial AgentsBacterial ProteinsTrans-ActivatorsVancomycin

Identifiers

PMID21968365
PMCPMC3232782
OpenAlexW2168783382

What OpenQuestion holds

Textmetadata
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.