ArticleNature communications2022
Targeting fungal membrane homeostasis with imidazopyrazoindoles impairs azole resistance and biofilm formation.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
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- Comparative Transcriptomic Analysis Reveals Cultivar-Dependent Resistance Responses toJournal of fungi (Basel, Switzerland) · 2026Article
- Uncovering actionable trade-offs of antifungal resistance in a yeast pathogen.Molecular systems biology · 2026Article
- Coniontins, lipopetaibiotics active against Candida auris identified from a microbial natural product fractionation library.Nature communications · 2025Article
- In Silico and In Vitro Potential Antifungal Insights of Insect-Derived Peptides in the Management ofInternational journal of molecular sciences · 2025Article
- Broad-Spectrum Activity and Mechanisms of Action of SQ109 on a Variety of Fungi.ACS infectious diseases · 2025Article
- Retinoids as Alternative Antifungal Agents AgainstMicroorganisms · 2025Article
- Structural and biochemical analysis of ligand binding in yeast Niemann-Pick type C1-related protein.Life science alliance · 2025Article
- Synergistic effects of dioscin and amphotericin B againstFrontiers in cellular and infection microbiology · 2025Article
- Response of Fusarium oxysporum soil isolate to amphotericin B and fluconazole at the proteomic level.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2024Article
- A synthetic peptide mimic kills Candida albicans and synergistically prevents infection.Nature communications · 2024Article
- Step-wise evolution of azole resistance through copy number variation followed by KSR1 loss of heterozygosity in Candida albicans.PLoS pathogens · 2024Article
- Erg251 has complex and pleiotropic effects on sterol composition, azole susceptibility, filamentation, and stress response phenotypes.PLoS pathogens · 2024Article
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- Andrographolide Induces ROS-Mediated Cytotoxicity, Lipid Peroxidation, and Compromised Cell Integrity inAntioxidants (Basel, Switzerland) · 2023Article
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- Azole potentiation in Candida species.PLoS pathogens · 2023Article
- The Metabolism of Susceptibility: Clearing the FoG Between Tolerance and Resistance inCurrent clinical microbiology reports · 2023Article
Corrections and comments
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Authors and funding
27 authors at 10 institutions in 3 countries.
Funding
Abstract
Fungal infections cause more than 1.5 million deaths annually. With an increase in immune-deficient susceptible populations and the emergence of antifungal drug resistance, there is an urgent need for novel strategies to combat these life-threatening infections. Here, we use a combinatorial screening approach to identify an imidazopyrazoindole, NPD827, that synergizes with fluconazole against azole-sensitive and -resistant isolates of Candida albicans. NPD827 interacts with sterols, resulting in profound effects on fungal membrane homeostasis and induction of membrane-associated stress responses. The compound impairs virulence in a Caenorhabditis elegans model of candidiasis, blocks C. albicans filamentation in vitro, and prevents biofilm formation in a rat model of catheter infection by C. albicans. Collectively, this work identifies an imidazopyrazoindole scaffold with a non-protein-targeted mode of action that re-sensitizes the leading human fungal pathogen, C. albicans, to azole antifungals.
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