Evidence map›Paper›PMID 24787619›Full record

ArticleGenome biology and evolution2014

Dissecting vancomycin-intermediate resistance in staphylococcus aureus using genome-wide association.

Md Tauqeer Alam, Robert A Petit, Emily K Crispell, Timothy A Thornton, Karen N Conneely, Yunxuan Jiang, Sarah W Satola, Timothy D Read

Abstract read
In one paragraph

Article in Genome biology and evolution, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
–field-weighted citation impact
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

78 citing papers in PubMed.

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  19. Vancomycin heteroresistance inFuture science OA · 2021
    Article
  20. Review

18 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.

Md Tauqeer AlamDivision of Infectious Diseases, Department of Medicine, Emory University School of Medicine.
Robert A PetitDivision of Infectious Diseases, Department of Medicine, Emory University School of Medicine.
Emily K CrispellDivision of Infectious Diseases, Department of Medicine, Emory University School of MedicineAtlanta Veterans Affairs Medical Center.
Timothy A ThorntonDepartment of Biostatistics, University of Washington.
Karen N ConneelyDepartment of Human Genetics, Emory University School of Medicine.
Yunxuan JiangDepartment of Human Genetics, Emory University School of MedicineDepartment of Biostatistics and Bioinformatics, Emory University School of Public Health.
Sarah W SatolaDivision of Infectious Diseases, Department of Medicine, Emory University School of MedicineAtlanta Veterans Affairs Medical Center.
Timothy D ReadDivision of Infectious Diseases, Department of Medicine, Emory University School of MedicineDepartment of Human Genetics, Emory University School of Medicine tread@emory.edu.

Funding

Statistical Methods for X-Chromosome Genetic DataP01GM099568 · NIGMS · UNIVERSITY OF WASHINGTON · PI WEIR, BRUCE S. · 2012 to 2016
$7.3M
Genetics of vancomycin intermediate resistance in S. aureusR56AI091827 · NIAID · EMORY UNIVERSITY · PI READ, TIMOTHY D. · 2011 to 2011
$740k
Statistical Methods for Cancer Genetic Association Studies with Hidden PopulationK01CA148958 · NCI · UNIVERSITY OF WASHINGTON · PI THORNTON, TIMOTHY ALVIN · 2010 to 2014
$682k
NCI NIH HHS K01 CA148958NIAID NIH HHS AI091827NIAID NIH HHS R56 AI091827NIGMS NIH HHS P01 GM099568
6 · The paper itself

Abstract

Vancomycin-intermediate Staphylococcus aureus (VISA) is currently defined as having minimal inhibitory concentration (MIC) of 4-8 µg/ml. VISA evolves through changes in multiple genetic loci with at least 16 candidate genes identified in clinical and in vitro-selected VISA strains. We report a whole-genome comparative analysis of 49 vancomycin-sensitive S. aureus and 26 VISA strains. Resistance to vancomycin was determined by broth microdilution, Etest, and population analysis profile-area under the curve (PAP-AUC). Genome-wide association studies (GWAS) of 55,977 single-nucleotide polymorphisms identified in one or more strains found one highly significant association (P = 8.78 E-08) between a nonsynonymous mutation at codon 481 (H481) of the rpoB gene and increased vancomycin MIC. Additionally, we used a database of public S. aureus genome sequences to identify rare mutations in candidate genes associated with VISA. On the basis of these data, we proposed a preliminary model called ECM+RMCG for the VISA phenotype as a benchmark for future efforts. The model predicted VISA based on the presence of a rare mutation in a set of candidate genes (walKR, vraSR, graSR, and agrA) and/or three previously experimentally verified mutations (including the rpoB H481 locus) with an accuracy of 81% and a sensitivity of 73%. Further, the level of resistance measured by both Etest and PAP-AUC regressed positively with the number of mutations present in a strain. This study demonstrated 1) the power of GWAS for identifying common genetic variants associated with antibiotic resistance in bacteria and 2) that rare mutations in candidate gene, identified using large genomic data sets, can also be associated with resistance phenotypes.

Indexed as

Bacterial ProteinsGenome-Wide Association StudyGenotypeHumansMicrobial Sensitivity TestsModels, GeneticMutationPhenotypePhylogenyPolymorphism, Single NucleotideStaphylococcus aureusVancomycinVancomycin ResistanceBacterial ProteinsVancomycinbacteriagenomicsphylogenywhole-genome sequencing

Identifiers

PMID24787619
PMCPMC4040999

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LicenceCC BY
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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.