ArticleEukaryotic cell2008
A gain-of-function mutation in the transcription factor Upc2p causes upregulation of ergosterol biosynthesis genes and increased fluconazole resistance in a clinical Candida albicans isolate.
Article in Eukaryotic cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
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.
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.
Who cites it
126 citing papers in PubMed.
- Lipid-Based Drug Delivery Systems as Emerging Tools to Overcome Antifungal Resistance.International journal of molecular sciences · 2026Review
- Relative contributions of the ERG11Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2026Article
- Recurrent mutations in the stress regulator Cap1 reveal a trade-off between azole resistance and oxidative stress response in Candida albicans.PLoS biology · 2026Article
- Butyrolactol A enhances caspofungin efficacy via flippase inhibition in drug-resistant fungi.Cell · 2026Article
- Advances in vulvovaginal candidiasis research: a comprehensive review from epidemiology, diagnosis, treatment to resistance mechanisms.Frontiers in microbiology · 2026Review
- Article
- Mutations inAntimicrobial agents and chemotherapy · 2025Article
- Butyrolactol A potentiates caspofungin efficacy against resistant fungi via phospholipid flippase inhibition.bioRxiv : the preprint server for biology · 2025Article
- Understanding the mechanisms of resistance to azole antifungals inJAC-antimicrobial resistance · 2025Review
- The evolution of antifungal therapy: Traditional agents, current challenges and future perspectives.Current research in microbial sciences · 2025Review
- Dual inhibition of ERG11 and CDR2 in drug-resistantFrontiers in pharmacology · 2025Article
- Is there a difference in the expression levels of genes responsible for fluconazole resistance inCurrent medical mycology · 2025Review
- Genomics insights of candidiasis: mechanisms of pathogenicity and drug resistance.Frontiers in microbiology · 2025Review
- Unveiling the roles ofVirulence · 2024Article
- Article
- Adaptation of Candida albicans to specific host environments by gain-of-function mutations in transcription factors.PLoS pathogens · 2024Review
- The zinc cluster transcription factor Znc1 regulates Rta3-dependent miltefosine resistance inmSphere · 2024Article
- Probing gene function inmSphere · 2024Article
- Erg251 has complex and pleiotropic effects on sterol composition, azole susceptibility, filamentation, and stress response phenotypes.PLoS pathogens · 2024Article
- Insights into the structure, function, and impact ofCurrent medical mycology · 2024Review
66 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
In the pathogenic yeast Candida albicans, the zinc cluster transcription factor Upc2p has been shown to regulate the expression of ERG11 and other genes involved in ergosterol biosynthesis upon exposure to azole antifungals. ERG11 encodes lanosterol demethylase, the target enzyme of this antifungal class. Overexpression of UPC2 reduces azole susceptibility, whereas its disruption results in hypersusceptibility to azoles and reduced accumulation of exogenous sterols. Overexpression of ERG11 leads to the increased production of lanosterol demethylase, which contributes to azole resistance in clinical isolates of C. albicans, but the mechanism for this has yet to be determined. Using genome-wide gene expression profiling, we found UPC2 and other genes involved in ergosterol biosynthesis to be coordinately upregulated with ERG11 in a fluconazole-resistant clinical isolate compared with a matched susceptible isolate from the same patient. Sequence analysis of the UPC2 alleles of these isolates revealed that the resistant isolate contained a single-nucleotide substitution in one UPC2 allele that resulted in a G648D exchange in the encoded protein. Introduction of the mutated allele into a drug-susceptible strain resulted in constitutive upregulation of ERG11 and increased resistance to fluconazole. By comparing the gene expression profiles of the fluconazole-resistant isolate and of strains carrying wild-type and mutated UPC2 alleles, we identified target genes that are controlled by Upc2p. Here we show for the first time that a gain-of-function mutation in UPC2 leads to the increased expression of ERG11 and imparts resistance to fluconazole in clinical isolates of C. albicans.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.