Evidence map›Paper›PMID 29477713›Full record

ArticleFungal genetics and biology : FG & B2018

In-host microevolution of Aspergillus fumigatus: A phenotypic and genotypic analysis.

Eloise Ballard, Willem J G Melchers, Jan Zoll, Alistair J P Brown, Paul E Verweij, Adilia Warris

Open access · hybridAbstract read
In one paragraph

Article in Fungal genetics and biology : FG & B, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
6.6field-weighted citation impact, top 2% 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

66 citing papers in PubMed, 80 citations in OpenAlex.

  1. Accelerated mutator phenotype in a clinicalEmerging microbes & infections · 2026
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  7. A long non-coding RNA,bioRxiv : the preprint server for biology · 2026
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  8. Pathogenesis and Triazole Resistance inInfection and drug resistance · 2026
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  10. Pan-azole- and multi-fungicide-resistantApplied and environmental microbiology · 2024
    Article
  11. Multi-Locus Microsatellite Typing of Colonising and InvasiveJournal of fungi (Basel, Switzerland) · 2024
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  12. Journal of fungi (Basel, Switzerland) · 2024
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  13. Review
  14. Review
  15. Genomic Epidemiology Identifies Azole Resistance Due to TRJournal of fungi (Basel, Switzerland) · 2023
    Article
  16. Article
  17. Article
  18. Review
  19. Metabolic Plasticity and Virulence-Associated Factors ofJournal of fungi (Basel, Switzerland) · 2023
    Article
  20. Fungal Drug Response and Antimicrobial Resistance.Journal of fungi (Basel, Switzerland) · 2023
    Review

6 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

6 authors at 3 institutions in 2 countries.

Eloise BallardMedical Research Council Centre for Medical Mycology at the University of Aberdeen, Aberdeen Fungal Group, Institute of Medical Sciences, Aberdeen, UK.
Willem J G MelchersDepartment of Medical Microbiology, Radboud University Medical Centre, Nijmegen, The Netherlands; Centre of Expertise in Mycology, Radboudumc/CWZ, Nijmegen, The Netherlands.
Jan ZollDepartment of Medical Microbiology, Radboud University Medical Centre, Nijmegen, The Netherlands; Centre of Expertise in Mycology, Radboudumc/CWZ, Nijmegen, The Netherlands.
Alistair J P BrownMedical Research Council Centre for Medical Mycology at the University of Aberdeen, Aberdeen Fungal Group, Institute of Medical Sciences, Aberdeen, UK.
Paul E VerweijDepartment of Medical Microbiology, Radboud University Medical Centre, Nijmegen, The Netherlands; Centre of Expertise in Mycology, Radboudumc/CWZ, Nijmegen, The Netherlands.
Adilia WarrisMedical Research Council Centre for Medical Mycology at the University of Aberdeen, Aberdeen Fungal Group, Institute of Medical Sciences, Aberdeen, UK. Electronic address: a.warris@abdn.ac.uk.
University of Aberdeen · GBRadboud University Nijmegen · NLRadboud University Medical Center · NL

Funding

Biotechnology and Biological Sciences Research Council BB/K017365/1Medical Research Council MR/M026663/1Medical Research Council MR/N006364/1Wellcome TrustWellcome Trust 097377
6 · The paper itself

Abstract

In order to survive, Aspergillus fumigatus must adapt to specific niche environments. Adaptation to the human host includes modifications facilitating persistent colonisation and the development of azole resistance. The aim of this study is to advance understanding of the genetic and physiological adaptation of A. fumigatus in patients during infection and treatment. Thirteen A. fumigatus strains were isolated from a single chronic granulomatous disease patient suffering from persistent and recurrent invasive aspergillosis over a period of 2 years. All strains had identical microsatellite genotypes and were considered isogenic. Whole genome comparisons identified 248 non-synonymous single nucleotide polymorphisms. These non-synonymous mutations have potential to play a role in in-host adaptation. The first 2 strains isolated were azole susceptible, whereas later isolates were itraconazole, voriconazole and/or posaconazole resistant. Growth assays in the presence and absence of various antifungal stressors highlighted minor changes in growth rate and stress resistance, with exception of one isolate showing a significant growth defect. Poor conidiation was observed in later isolates. In certain drug resistant isolates conidiation was restored in the presence of itraconazole. Differences in virulence were observed as demonstrated in a Galleria mellonella infection model. We conclude that the microevolution of A. fumigatus in this patient has driven the emergence of both Cyp51A-independent and Cyp51A-dependent, azole resistance mechanisms, and additional phenotypes that are likely to have promoted fungal persistence.

Indexed as

Evolution, MolecularAdaptation, PhysiologicalAntifungal AgentsAspergillosisAspergillus fumigatusAzolesCytochrome P-450 Enzyme SystemDrug Resistance, FungalFungal ProteinsGenotypeGranulomatous Disease, ChronicHost-Pathogen InteractionsHumansMicrobial Sensitivity TestsMicrosatellite RepeatsPhenotypeAntifungal AgentsAzolesCytochrome P-450 Enzyme SystemFungal ProteinsAspergillus fumigatusAzole-resistanceFungal growthIn-host microevolutionWhole genome sequencing

Identifiers

PMID29477713
PMCPMC5883321
OpenAlexW2785599731

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.