Evidence map›Paper›PMID 30629653›Full record

ArticlePloS one2019

Analysis of antifungal resistance genes in Candida albicans and Candida glabrata using next generation sequencing.

Kathrin Spettel, Wolfgang Barousch, Athanasios Makristathis, Iris Zeller, Marion Nehr, Brigitte Selitsch, Michaela Lackner, Peter-Michael Rath, Joerg Steinmann, Birgit Willinger

Abstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 1 pooled it
–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

55 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  11. Genetic engineering in diatoms: advances and prospects.The Plant journal : for cell and molecular biology · 2025
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  18. Molecular Evaluation of the mRNA Expression of theJournal of fungi (Basel, Switzerland) · 2024
    Article
  19. Article
  20. Microbiology and molecular biology reviews : MMBR · 2024
    Review
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

10 authors.

Kathrin SpettelDepartment of Laboratory Medicine, Division of Clinical Microbiology, Medical University of Vienna, Vienna, Austria.ORCID 0000-0002-8901-8770
Wolfgang BarouschDepartment of Laboratory Medicine, Division of Clinical Microbiology, Medical University of Vienna, Vienna, Austria.
Athanasios MakristathisDepartment of Laboratory Medicine, Division of Clinical Microbiology, Medical University of Vienna, Vienna, Austria.
Iris ZellerDepartment of Laboratory Medicine, Division of Clinical Microbiology, Medical University of Vienna, Vienna, Austria.
Marion NehrDepartment of Laboratory Medicine, Division of Clinical Microbiology, Medical University of Vienna, Vienna, Austria.
Brigitte SelitschDepartment of Laboratory Medicine, Division of Clinical Microbiology, Medical University of Vienna, Vienna, Austria.
Michaela LacknerDivision of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
Peter-Michael RathInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Joerg SteinmannInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Birgit WillingerDepartment of Laboratory Medicine, Division of Clinical Microbiology, Medical University of Vienna, Vienna, Austria.ORCID 0000-0001-7921-5749

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

INTRODUCTION/

objectivesAn increase in antifungal resistant Candida strains has been reported in recent years. The aim of this study was to detect mutations in resistance genes of azole-resistant, echinocandin-resistant or multi-resistant strains using next generation sequencing technology, which allows the analysis of multiple resistance mechanisms in a high throughput setting.

methodsForty clinical Candida isolates (16 C. albicans and 24 C. glabrata strains) with MICs for azoles and echinocandins above the clinical EUCAST breakpoint were examined. The genes ERG11, ERG3, TAC1 and GSC1 (FKS1) in C. albicans, as well as ERG11, CgPDR1, FKS1 and FKS2 in C. glabrata were sequenced.

resultsFifty-four different missense mutations were identified, 13 of which have not been reported before. All nine echinocandin-resistant Candida isolates showed mutations in the hot spot (HS) regions of FKS1, FKS2 or GSC1. In ERG3 two homozygous premature stop codons were identified in two highly azole-resistant and moderately echinocandin-resistant C. albicans strains. Seven point mutations in ERG11 were determined in azole-resistant C. albicans whereas in azole-resistant C. glabrata, no ERG11 mutations were detected. In 10 out of 13 azole-resistant C. glabrata, 12 different potential gain-of-function mutations in the transcription factor CgPDR1 were verified, which are associated with an overexpression of the efflux pumps CDR1/2.

conclusionThis study showed that next generation sequencing allows the thorough investigation of a large number of isolates more cost efficient and faster than conventional Sanger sequencing. Targeting different resistance genes and a large sample size of highly resistant strains allows a better determination of the relevance of the different mutations, and to differentiate between causal mutations and polymorphisms.

Indexed as

Antifungal AgentsCandida albicansCandida glabrataComputational BiologyDrug Resistance, FungalMicrobial Sensitivity TestsMutationSequence Analysis, DNAAntifungal Agents

Identifiers

PMID30629653
PMCPMC6328131

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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.