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Record W4318195451 · doi:10.1101/2023.01.24.524502

The Adr1 transcription factor directs regulation of the ergosterol pathway and azole resistance in C. <i>albicans</i>

2023· preprint· en· W4318195451 on OpenAlexafffund
Manjari Shrivastava, Gaëlle S. Kouyoumdjian, Eftyhios Kirbizakis, Daniel Ruiz, Manon Henry, Antony T. Vincent, Adnane Sellam, Malcolm Whiteway

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2023
Typepreprint
Languageen
FieldMedicine
TopicAntifungal resistance and susceptibility
Canadian institutionsUniversité de MontréalConcordia UniversityUniversité LavalMontreal Heart Institute
FundersNatural Sciences and Engineering Research Council of CanadaConcordia University
KeywordsCandida albicansTranscription factorErgosterolZinc finger transcription factorCorpus albicansBiochemistryBiologySaccharomyces cerevisiaeChemistryCell biologyZinc fingerGeneMicrobiology

Abstract

fetched live from OpenAlex

Abstract Transcription factors play key roles in cellular regulation and are critical in the control of drug resistance in the fungal pathogen Candida albicans . We found that activation of the transcription factor C4_02500C_A (Adr1) conferred significant resistance against fluconazole. In Saccharomyces cerevisiae , Adr1 is a carbon-source-responsive zinc-finger transcription factor required for transcription of the glucose-repressed gene ADH1 and of genes required for ethanol, glycerol, and fatty acid utilization. Motif scanning of promoter elements suggests that Adr1 may be rewired in fungi and governs the ergosterol synthesis pathway in C. albicans . Because previous studies have identified the zinc-cluster transcription factor Upc2 as a regulator of the ergosterol pathway in both fungi, we examined the relationship of Adr1 and Upc2 in sterol biosynthesis in C. albicans . Phenotypic profiles of either ADR1 and UPC2 modulation in C. albicans showed differential growth in the presence of fluconazole; either adr1 or upc2 homozygous deletion results in sensitivity to the drug while their activation generates a fluconazole resistant strain. The rewiring from ergosterol synthesis to fatty acid metabolism involved all members of the Adr1 regulon except the alcohol dehydrogenase Adh1, which remains under Adr1 control in both circuits and may have been driven by the lifestyle of S. cerevisiae , which requires the ability to both tolerate and process high concentrations of ethanol.

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)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.019
GPT teacher head0.227
Teacher spread0.208 · 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 designBench or experimental
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

Citations2
Published2023
Admission routes2
Has abstractyes

Explore more

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