ArticlemBio2022
Antagonism of the Azoles to Olorofim and Cross-Resistance Are Governed by Linked Transcriptional Networks in Aspergillus fumigatus.
Article in mBio, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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
20 citing papers in PubMed, 25 citations in OpenAlex.
- Olorofim in combination with azole antifungals: results from the Phase 2 salvage therapy study.The Journal of antimicrobial chemotherapy · 2026Trial
- In Vitro Evaluation of Olorofim and Amphotericin B Combination Therapy AgainstJournal of fungi (Basel, Switzerland) · 2026Article
- Challenges and opportunities in the management of severe pneumonia. Key concepts from the Seventh Annual Meeting of Spanish Experts 2025.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2026Review
- Comment on: Antagonistic in vitro interaction between olorofim and voriconazole against Aspergillus fumigatus.The Journal of antimicrobial chemotherapy · 2026Article
- Article
- Current and emerging therapies for fungal biofilms and systemic infections.Critical reviews in microbiology · 2026Review
- Compassionate Use of Olorofim for Invasive Mold Infections: A Nationwide Observational Study in France.Open forum infectious diseases · 2026Article
- Marker-Free CRISPR/Cas9 RNP Transformation for Gene Disruption in Aspergillus fumigatus.Methods in molecular biology (Clifton, N.J.) · 2026Article
- A quiet but growing threat: Global perspectives on antifungal resistance and future therapeutic approaches.Indian journal of pharmacology · 2026Review
- Antifungal treatment strategies and their impact on resistance development in clinical settings.The Journal of antimicrobial chemotherapy · 2025Review
- Antagonistic interaction between posaconazole and olorofim in a murine model of invasive pulmonary aspergillosis.The Journal of antimicrobial chemotherapy · 2025Article
- In vitro evaluation of olorofim and antifungal combinations against Aspergillus and Candida species.The Journal of antimicrobial chemotherapy · 2025Article
- Azole-ResistantJournal of fungi (Basel, Switzerland) · 2025Review
- Review
- Innovative antifungal strategies to combat drug-resistantFrontiers in cellular and infection microbiology · 2025Review
- Novel antifungals and treatment approaches to tackle resistance and improve outcomes of invasive fungal disease.Clinical microbiology reviews · 2024Review
- Functional analysis of the Aspergillus fumigatus kinome identifies a druggable DYRK kinase that regulates septal plugging.Nature communications · 2024Article
- The Role of Olorofim in the Treatment of Filamentous Fungal Infections: A Review of In Vitro and In Vivo Studies.Journal of fungi (Basel, Switzerland) · 2024Review
- Aspergillus fumigatus strains that evolve resistance to the agrochemical fungicide ipflufenoquin in vitro are also resistant to olorofim.Nature microbiology · 2024Article
- Invasive Fungal Disease in Allogeneic Hematopoietic Cell Transplantation: New Risk Factors and New Therapeutic Options in a Changing World.Transplant infectious disease : an official journal of the Transplantation SocietyReview
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
Aspergillosis, in its various manifestations, is a major cause of morbidity and mortality. Very few classes of antifungal drugs have been approved for clinical use to treat these diseases and resistance to the first-line therapeutic class, the triazoles are increasing. A new class of antifungals that target pyrimidine biosynthesis, the orotomides, are currently in development with the first compound in this class, olorofim in late-stage clinical trials. In this study, we identified an antagonistic action of the triazoles on the action of olorofim. We showed that this antagonism was the result of an azole-induced upregulation of the pyrimidine biosynthesis pathway. Intriguingly, we showed that loss of function in the higher order transcription factor, HapB a member of the heterotrimeric HapB/C/E (CBC) complex or the regulator of nitrogen metabolic genes AreA, led to cross-resistance to both the azoles and olorofim, indicating that factors that govern resistance were under common regulatory control. However, the loss of azole-induced antagonism required decoupling of the pyrimidine biosynthetic pathway in a manner independent of the action of a single transcription factor. Our study provided evidence for complex transcriptional crosstalk between the pyrimidine and ergosterol biosynthetic pathways.
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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.