Evidence map›Paper›PMID 30626317›Full record

ArticleBMC genomics2019

Phenotypic plasticity and the evolution of azole resistance in Aspergillus fumigatus; an expression profile of clinical isolates upon exposure to itraconazole.

Margriet W J Hokken, Jan Zoll, Jordy P M Coolen, Bas J Zwaan, Paul E Verweij, Willem J G Melchers

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

21 citing papers in PubMed, 37 citations in OpenAlex.

  1. Accelerated mutator phenotype in a clinicalEmerging microbes & infections · 2026
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  2. Article
  3. Genotype-Phenotype Relationships in Azole-ResistantJournal of fungi (Basel, Switzerland) · 2026
    Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. The Transcriptome Response to Azole Compounds inJournal of fungi (Basel, Switzerland) · 2023
    Article
  9. Article
  10. Deletion ofAntimicrobial agents and chemotherapy · 2022
    Article
  11. Growth ofJournal of fungi (Basel, Switzerland) · 2022
    Review
  12. Antifungal mechanism of (Frontiers in microbiology · 2022
    Article
  13. Article
  14. Studies in mycology · 2021
    Review
  15. Transcriptomic studies on Purpureocillium lilacinum reveal molecular mechanisms of response to fluconazole and itraconazole.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2021
    Article
  16. Article
  17. Molecular Epidemiology ofJournal of fungi (Basel, Switzerland) · 2021
    Review
  18. A Cyp51B Mutation Contributes to Azole Resistance inJournal of fungi (Basel, Switzerland) · 2020
    Article
  19. Article
  20. Article
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 1 institution in 1 country.

Margriet W J HokkenDepartment of Medical Microbiology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, the Netherlands. margriet.hokken@radboudumc.nl.
Jan ZollDepartment of Medical Microbiology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, the Netherlands.
Jordy P M CoolenDepartment of Medical Microbiology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, the Netherlands.
Bas J ZwaanDepartment of Plant Sciences, Laboratory of Genetics, Wageningen University, Droevendaalsesteeg 1, 6708PB, Wageningen, The Netherlands.
Paul E VerweijDepartment of Medical Microbiology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, the Netherlands.
Willem J G MelchersDepartment of Medical Microbiology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, the Netherlands.
Radboud University Medical Center · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe prevalence of azole resistance in clinical and environmental Aspergillus fumigatus isolates is rising over the past decades, but the molecular basis of the development of antifungal drug resistance is not well understood. This study focuses on the role of phenotypic plasticity in the evolution of azole resistance in A. fumigatus. When A. fumigatus is challenged with a new stressful environment, phenotypic plasticity may allow A. fumigatus to adjust their physiology to still enable growth and reproduction, therefore allowing the establishment of genetic adaptations through natural selection on the available variation in the mutational and recombinational gene pool. To investigate these short-term physiological adaptations, we conducted time series transcriptome analyses on three clinical A. fumigatus isolates, during incubation with itraconazole.

resultsAfter analysis of expression patterns, we identified 3955, 3430, 1207, and 1101 differentially expressed genes (DEGs), after 30, 60, 120 and 240 min of incubation with itraconazole, respectively. We explored the general functions in these gene groups and we identified 186 genes that were differentially expressed during the whole time series. Additionally, we investigated expression patterns of potential novel drug-efflux transporters, genes involved in ergosterol and phospholipid biosynthesis, and the known MAPK proteins of A. fumigatus.

conclusionsOur data suggests that A. fumigatus adjusts its transcriptome quickly within 60 min of exposure to itraconazole. Further investigation of these short-term adaptive phenotypic plasticity mechanisms might enable us to understand how the direct response of A. fumigatus to itraconazole promotes survival of the fungus in the patient, before any "hard-wired" genetic mutations arise.

Indexed as

Adaptation, PhysiologicalAntifungal AgentsAspergillosisAspergillus fumigatusAzolesDrug Resistance, FungalGene Expression Regulation, FungalHumansItraconazoleMicrobial Sensitivity TestsMutationAntifungal AgentsAzolesItraconazoleAspergillus fumigatusAzole resistanceItraconazolePhenotypic plasticityRNA-seq

Identifiers

PMID30626317
PMCPMC6327609
OpenAlexW2908726623

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LicenceCC BY
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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.