ArticleMolecular systems biology2011
Cross-species discovery of syncretic drug combinations that potentiate the antifungal fluconazole.
Article in Molecular systems biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03112031 (A Randomized Trial of Tamoxifen Combined With Amphotericin B and Fluconazole for Cryptococcal Meningitis), which is not on this map. Cited by 106 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.
A Randomized Trial of Tamoxifen Combined With Amphotericin B and Fluconazole for Cryptococcal Meningitis
Who cites it
106 citing papers in PubMed, 183 citations in OpenAlex.
- Efficacy of adjunctive sertraline for the treatment of HIV-associated cryptococcal meningitis: an open-label dose-ranging study.The Lancet. Infectious diseases · 2016Trial
- Anti-psychotic drugs act synergistically in combination with antifungal drugs to inhibit drug-resistantmSphere · 2026Article
- NMD-mediated control of Tor influences adaptation to nutrient and temperature conditions inbioRxiv : the preprint server for biology · 2026Article
- Advances in cryptococcal infections-associated immunopathology and potential therapeutic strategies.Frontiers in pharmacology · 2026Review
- The dual role of sertraline: From antidepressant to antifungal drug with broad metabolic disruption.Genetics and molecular biology · 2026Article
- A screen to identify antifungal antagonists reveals a variety of pharmacotherapies that induce echinocandin tolerance inAntimicrobial agents and chemotherapy · 2025Article
- Bioluminescent Pseudomonas aeruginosa and Escherichia coli for whole-cell screening of antibacterial and adjuvant compounds.Scientific reports · 2024Article
- Review
- The atypical antipsychotic aripiprazole alters the outcome of disseminatedInfection and immunity · 2024Article
- Pitavastatin Calcium Confers Fungicidal Properties to Fluconazole by Inhibiting Ubiquinone Biosynthesis and Generating Reactive Oxygen Species.Antioxidants (Basel, Switzerland) · 2024Article
- Wiring Between Close Nodes in Molecular Networks Evolves More Quickly Than Between Distant Nodes.Molecular biology and evolution · 2024Article
- The atypical antipsychotic aripiprazole alters the outcome of disseminatedbioRxiv : the preprint server for biology · 2024Article
- Halofantrine Hydrochloride Acts as an Antioxidant Ability Inhibitor That Enhances Oxidative Stress Damage toAntioxidants (Basel, Switzerland) · 2024Article
- Strategies of Pharmacological Repositioning for the Treatment of Medically Relevant Mycoses.Infection and drug resistance · 2024Review
- Molecular Pathway, Epidemiological Data and Treatment Strategies of Fungal Infection (Mycoses): A Comprehensive Review.Central nervous system agents in medicinal chemistry · 2024Review
- Proteasome inhibition as a therapeutic target for the fungal pathogenMicrobiology spectrum · 2023Article
- Anti-Candidal Activity of Reboxetine and Sertraline Antidepressants: Effects on Pre-Formed Biofilms.Antibiotics (Basel, Switzerland) · 2023Article
- Small molecules for combating multidrug-resistant superbugActa pharmaceutica Sinica. B · 2022Review
- Genomic Approaches to Antifungal Drug Target Identification and Validation.Annual review of microbiology · 2022Review
- Review
46 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
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Resistance to widely used fungistatic drugs, particularly to the ergosterol biosynthesis inhibitor fluconazole, threatens millions of immunocompromised patients susceptible to invasive fungal infections. The dense network structure of synthetic lethal genetic interactions in yeast suggests that combinatorial network inhibition may afford increased drug efficacy and specificity. We carried out systematic screens with a bioactive library enriched for off-patent drugs to identify compounds that potentiate fluconazole action in pathogenic Candida and Cryptococcus strains and the model yeast Saccharomyces. Many compounds exhibited species- or genus-specific synergism, and often improved fluconazole from fungistatic to fungicidal activity. Mode of action studies revealed two classes of synergistic compound, which either perturbed membrane permeability or inhibited sphingolipid biosynthesis. Synergistic drug interactions were rationalized by global genetic interaction networks and, notably, higher order drug combinations further potentiated the activity of fluconazole. Synergistic combinations were active against fluconazole-resistant clinical isolates and an in vivo model of Cryptococcus infection. The systematic repurposing of approved drugs against a spectrum of pathogens thus identifies network vulnerabilities that may be exploited to increase the activity and repertoire of antifungal agents.
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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.