ArticleNature communications2024
Toxic eburicol accumulation drives the antifungal activity of azoles against Aspergillus fumigatus.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed.
- The AP-1 adaptor complex is required for cell surface modifications and the survival ofInfection and immunity · 2026Article
- Early Cellular Responses ofAntibiotics (Basel, Switzerland) · 2026Article
- Lanosterol synthase inhibition as a potential approach for re-sensitizing triazole-resistantmBio · 2026Article
- Ergosterol from Yeasts PromotesInternational journal of molecular sciences · 2026Article
- Iron starvation confers azole tolerance inmBio · 2026Article
- Rho2-dependent cell wall remodeling boosts the fungistatic activity of manogepix againstCell surface (Amsterdam, Netherlands) · 2026Article
- Lipid-Based Drug Delivery Systems as Emerging Tools to Overcome Antifungal Resistance.International journal of molecular sciences · 2026Review
- RTA-like proteins regulate azole susceptibility by affecting the expression of the oxidoreductase gene oxrA in Aspergillus fumigatus.BMC microbiology · 2026Article
- Directed evolution of the pathogenic moldAntimicrobial agents and chemotherapy · 2026Article
- Antifungal efficacy of linoleic-acid-rich Cucurbita pepo L. seed oil revealed by GC-MS profiling of lipids and bioactive markers, ergosterol depletion, and network pharmacology.BMC microbiology · 2026Article
- Article
- A Novel Erg3 T208Is Substitution Associated with Reduced Fluconazole and Voriconazole Susceptibility in ClinicalInfection and drug resistance · 2026Article
- Rising antifungal resistance inFrontiers in microbiology · 2026Review
- Review
- HyperdCas12a-based multiplexed genetic regulation in Candida albicans.Nucleic acids research · 2025Article
- Targeted regulation of sterol biosynthesis genes according to perturbations in ergosterol biosynthesis in fungi.Journal of advanced research · 2025Article
- Article
- Evaluation of the efficacy of combination therapy in the treatment of fungal otitis externa.Scientific reports · 2025Article
- Article
- Significant Impact of Growth Medium on Itraconazole Susceptibility in Azole-Resistant Versus Wild-TypeInternational journal of molecular sciences · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
Azole antifungals inhibit the sterol C14-demethylase (CYP51/Erg11) of the ergosterol biosynthesis pathway. Here we show that the azole-induced synthesis of fungicidal cell wall carbohydrate patches in the pathogenic mold Aspergillus fumigatus strictly correlates with the accumulation of the CYP51 substrate eburicol. A lack of other essential ergosterol biosynthesis enzymes, such as sterol C24-methyltransferase (Erg6A), squalene synthase (Erg9) or squalene epoxidase (Erg1) does not trigger comparable cell wall alterations. Partial repression of Erg6A, which converts lanosterol into eburicol, increases azole resistance. The sterol C5-desaturase (ERG3)-dependent conversion of eburicol into 14-methylergosta-8,24(28)-dien-3β,6α-diol, the "toxic diol" responsible for the fungistatic activity against yeasts, is not required for the fungicidal effects in A. fumigatus. While ERG3-lacking yeasts are azole resistant, ERG3-lacking A. fumigatus becomes more susceptible. Mutants lacking mitochondrial complex III functionality, which are much less effectively killed, but strongly inhibited in growth by azoles, convert eburicol more efficiently into the supposedly "toxic diol". We propose that the mode of action of azoles against A. fumigatus relies on accumulation of eburicol which exerts fungicidal effects by triggering cell wall carbohydrate patch formation.
Indexed as
Identifiers
What Socratic 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 Socratic graph.