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Record W4224669774 · doi:10.1038/s41564-022-01091-2

Population genomics confirms acquisition of drug-resistant Aspergillus fumigatus infection by humans from the environment

2022· article· en· W4224669774 on OpenAlexfundno aff
Johanna Rhodes, Alireza Abdolrasouli, Katie Dunne, Thomas R. Sewell, Yuyi Zhang, Eloise Ballard, Amelie P. Brackin, Norman van Rhijn, Harry Chown, Alexandra Tsitsopoulou, Raquel Posso, Sanjay H. Chotirmall, Noel G. McElvaney, Philip G. Murphy, Alida Fe Talento, J. A. A. Renwick, Paul S. Dyer, Adrien Székely, Paul Bowyer, Michael Bromley, Elizabeth M. Johnson, P. Lewis White, Adilia Warris, Richard Barton, Silke Schelenz, Thomas R. Rogers, Darius Armstrong‐James, Matthew C. Fisher

Bibliographic record

VenueNature Microbiology · 2022
Typearticle
Languageen
FieldMedicine
TopicAntifungal resistance and susceptibility
Canadian institutionsnot available
FundersNatural Environment Research CouncilMedical Research CouncilDirectorate for Biological SciencesMedical Research Council Centre for Medical MycologyTrinity College DublinWellcomeImperial College LondonResearch Councils UKBiotechnology and Biological Sciences Research CouncilUniversity of ExeterCystic Fibrosis TrustDepartment of Health and Social CareNational Institute for Health and Care ResearchGilead SciencesSight Research UKWellcome TrustCanadian Institute for Advanced Research
KeywordsBiologyAspergillus fumigatusDrug resistancePopulationGeneticsAntifungal drugGenomeAzoleGeneCladeGenotypeMicrobiologyCandida albicansAntifungalPhylogeneticsMedicine

Abstract

fetched live from OpenAlex

Infections caused by the fungal pathogen Aspergillus fumigatus are increasingly resistant to first-line azole antifungal drugs. However, despite its clinical importance, little is known about how susceptible patients acquire infection from drug-resistant genotypes in the environment. Here, we present a population genomic analysis of 218 A. fumigatus isolates from across the UK and Ireland (comprising 153 clinical isolates from 143 patients and 65 environmental isolates). First, phylogenomic analysis shows strong genetic structuring into two clades (A and B) with little interclade recombination and the majority of environmental azole resistance found within clade A. Second, we show occurrences where azole-resistant isolates of near-identical genotypes were obtained from both environmental and clinical sources, indicating with high confidence the infection of patients with resistant isolates transmitted from the environment. Third, genome-wide scans identified selective sweeps across multiple regions indicating a polygenic basis to the trait in some genetic backgrounds. These signatures of positive selection are seen for loci containing the canonical genes encoding fungicide resistance in the ergosterol biosynthetic pathway, while other regions under selection have no defined function. Lastly, pan-genome analysis identified genes linked to azole resistance and previously unknown resistance mechanisms. Understanding the environmental drivers and genetic basis of evolving fungal drug resistance needs urgent attention, especially in light of increasing numbers of patients with severe viral respiratory tract infections who are susceptible to opportunistic fungal superinfections.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.005
GPT teacher head0.226
Teacher spread0.221 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations240
Published2022
Admission routes1
Has abstractyes

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