ArticleNature microbiology2022
Uncontrolled transposition following RNAi loss causes hypermutation and antifungal drug resistance in clinical isolates of Cryptococcus neoformans.
Article in Nature microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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42 citing papers in PubMed, 49 citations in OpenAlex.
- An ancestral mitochondrial DNA insertion disrupts RNAi and enables persistence of a novel mycovirus inbioRxiv : the preprint server for biology · 2026Article
- Aneuploidy promotes transient stress adaptation and metabolic flexibility in the human fungal pathogen Aspergillus fumigatus.Current biology : CB · 2026Article
- Innovation in antifungal therapy.EMBO molecular medicine · 2026Review
- Genetic Variability and Aggressiveness ofPlants (Basel, Switzerland) · 2026Article
- Variable ectopic heterochromatin islands provide an alternative route to antifungal heteroresistance inbioRxiv : the preprint server for biology · 2026Article
- Primary Cryptococcal Cellulitis With High Antigenemia in an Immunocompromised Host: A Case Report and Laboratory Investigation of the CausativeOpen forum infectious diseases · 2026Article
- The dynamics of transposable element content in the genome of the human pathogen Histoplasma.Fungal genetics and biology : FG & B · 2026Article
- MycoMobilome: a community-focused non-redundant database of transposable element consensus sequences for the fungal kingdom.NAR genomics and bioinformatics · 2026Article
- Epimutations driven by RNAi or heterochromatin evoke transient antimicrobial drug resistance in pathogenic Mucor fungi.PLoS biology · 2026Article
- Temperature and genetic background drive mobilization of diverse transposable elements in a global human fungal pathogen.PLoS genetics · 2026Article
- Epimutations driven by RNAi or heterochromatin evoke transient antimicrobial drug resistance in fungi.bioRxiv : the preprint server for biology · 2025Article
- Genomic and phenotypic insights into the expanding phylogenetic landscape of the Cryptococcus genus.PLoS genetics · 2025Article
- Genomic and phenotypic insights into the expanding phylogenetic landscape of thebioRxiv : the preprint server for biology · 2025Article
- Unisexual reproduction in the global human fungal pathogenProceedings of the National Academy of Sciences of the United States of America · 2025Article
- The complex evolution and genomic dynamics of mating-type loci in Cryptococcus and Kwoniella.PLoS biology · 2025Article
- Whole-chromosome duplications drive antimicrobial resistance inbioRxiv : the preprint server for biology · 2025Article
- Unisexual reproduction in the global human fungal pathogenbioRxiv : the preprint server for biology · 2025Article
- Antifungal resistance: Emerging mechanisms and implications (Review).Molecular medicine reports · 2025Review
- Tracing the evolution and genomic dynamics of mating-type loci inbioRxiv : the preprint server for biology · 2025Article
- Immunomodulatory activity of Pleurotus pulmonarius crude extract to human monocyte against Cryptococcus neoformans.BMC complementary medicine and therapies · 2025Article
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7 authors at 2 institutions in 2 countries.
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Abstract
Cryptococcus neoformans infections cause approximately 15% of AIDS-related deaths owing to a combination of limited antifungal therapies and drug resistance. A collection of clinical and environmental C. neoformans isolates were assayed for increased mutation rates via fluctuation analysis, and we identified two hypermutator C. neoformans clinical isolates with increased mutation rates when exposed to the combination of rapamycin and FK506. Sequencing of drug target genes found that Cnl1 transposon insertions conferred the majority of resistance to rapamycin and FK506 and could also independently cause resistance to 5-fluoroorotic acid and the clinically relevant antifungal 5-flucytosine. Whole-genome sequencing revealed both hypermutator genomes harbour a nonsense mutation in the RNA-interference component ZNF3 and hundreds of Cnl1 elements organized into massive subtelomeric arrays on each of the fourteen chromosomes. Quantitative trait locus mapping in 28 progeny derived from a cross between a hypermutator and wild-type identified a locus associated with hypermutation that included znf3. CRISPR editing of the znf3 nonsense mutation abolished hypermutation and restored small-interfering-RNA production. We conclude that hypermutation and drug resistance in these clinical isolates result from RNA-interference loss and accumulation of Cnl1 elements.
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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.