ArticlePLoS genetics2019
Broad antifungal resistance mediated by RNAi-dependent epimutation in the basal human fungal pathogen Mucor circinelloides.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 69 citations in OpenAlex.
- Molecular Mechanisms, Diagnosis, and Therapeutic Strategies of Antifungal Resistance in Filamentous Fungi.Journal of fungi (Basel, Switzerland) · 2026Review
- Antifungal resistance: from classical mechanisms to the expanding role of acetyltransferases.Journal of biomedical science · 2026Review
- A long non-coding RNA,mSphere · 2026Article
- Variable ectopic heterochromatin islands provide an alternative route to antifungal heteroresistance inbioRxiv : the preprint server for biology · 2026Article
- Genetic and Epigenetic Mechanisms Underlying Reversible Adaptive Responses in Fungi.Journal of fungi (Basel, Switzerland) · 2026Review
- A long non-coding RNA,bioRxiv : the preprint server for biology · 2026Article
- Epimutations driven by RNAi or heterochromatin evoke transient antimicrobial drug resistance in pathogenic Mucor fungi.PLoS biology · 2026Article
- Epimutations driven by RNAi or heterochromatin evoke transient antimicrobial drug resistance in fungi.bioRxiv : the preprint server for biology · 2025Article
- Learning from fungicide resistance: Evolutionary insights to guide RNAi-based control of fungal crop pathogens.Fungal biology reviews · 2025Article
- RNAi epimutations conferring antifungal drug resistance are inheritable.Nature communications · 2025Article
- Celebrating the fifth edition of the International Symposium on Fungal Stress - ISFUS, a decade after its 2014 debut.Fungal biology · 2025Article
- The Dual PathogenJournal of fungi (Basel, Switzerland) · 2025Review
- Direct Targeted Degradation of Transposon RNAs by the Non-Canonical RNAi Pathway of the FungusInternational journal of molecular sciences · 2025Article
- A human-relevant alternative infection model for mucormycosis using the silkworm Bombyx mori.PloS one · 2025Article
- Comprehensive analysis of the mechanisms conferring resistance to phenamacril in theFrontiers in cellular and infection microbiology · 2025Review
- RNAi-Based Approaches to Control Mycotoxin Producers: Challenges and Perspectives.Journal of fungi (Basel, Switzerland) · 2024Review
- Symmetric and asymmetric DNA N6-adenine methylation regulates different biological responses in Mucorales.Nature communications · 2024Article
- Challenges and Opportunities Arising from Host-International journal of molecular sciences · 2024Review
- Antimicrobial resistance in the wild: Insights from epigenetics.Evolutionary applications · 2024Review
- Identification of an active RNAi pathway inProceedings of the National Academy of Sciences of the United States of America · 2024Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Mucormycosis-an emergent, deadly fungal infection-is difficult to treat, in part because the causative species demonstrate broad clinical antifungal resistance. However, the mechanisms underlying drug resistance in these infections remain poorly understood. Our previous work demonstrated that one major agent of mucormycosis, Mucor circinelloides, can develop resistance to the antifungal agents FK506 and rapamycin through a novel, transient RNA interference-dependent mechanism known as epimutation. Epimutations silence the drug target gene and are selected by drug exposure; the target gene is re-expressed and sensitivity is restored following passage without drug. This silencing process involves generation of small RNA (sRNA) against the target gene via core RNAi pathway proteins. To further elucidate the role of epimutation in the broad antifungal resistance of Mucor, epimutants were isolated that confer resistance to another antifungal agent, 5-fluoroorotic acid (5-FOA). We identified epimutant strains that exhibit resistance to 5-FOA without mutations in PyrF or PyrG, enzymes which convert 5-FOA into the active toxic form. Using sRNA hybridization as well as sRNA library analysis, we demonstrate that these epimutants harbor sRNA against either pyrF or pyrG, and further show that this sRNA is lost after reversion to drug sensitivity. We conclude that epimutation is a mechanism capable of targeting multiple genes, enabling Mucor to develop resistance to a variety of antifungal agents. Elucidation of the role of RNAi in epimutation affords a fuller understanding of mucormycosis. Furthermore, it improves our understanding of fungal pathogenesis and adaptation to stresses, including the evolution of drug resistance.
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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.