Evidence map›Paper›PMID 40775213›Full record

ArticleNature communications2025

RNAi epimutations conferring antifungal drug resistance are inheritable.

Carlos Pérez-Arques, María Isabel Navarro-Mendoza, Ziyan Xu, Grit Walther, Joseph Heitman

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Innovation in antifungal therapy.EMBO molecular medicine · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Carlos Pérez-Arques *Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA. carlos.parq@duke.edu.ORCID http://orcid.org/0000-0003-1384-3608
María Isabel Navarro-Mendoza *Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA. maria.navarrom@umh.es.ORCID http://orcid.org/0000-0002-3560-6155
Ziyan XuDepartment of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0009-0001-7055-9788
Grit WaltherNational Reference Center for Invasive Fungal Infections, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany.ORCID http://orcid.org/0000-0003-4030-4618
Joseph HeitmanDepartment of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA. heitm001@duke.edu.ORCID http://orcid.org/0000-0001-6369-5995

Funding

Structure, function, and evolution of the Cryptococcus MAT locusR01AI050113 · NIAID · DUKE UNIVERSITY · PI HEITMAN, JOSEPH · 2002 to 2024
$8.5M
ROLE OF CALCINEURIN IN C. NEOFORMANS MATING AND FRUITINGR01AI039115 · NIAID · DUKE UNIVERSITY · PI HEITMAN, JOSEPH · 1997 to 2025
$6.7M
RNAi-dependent epimutation roles in antimicrobial drug resistance and pathogenesisR01AI170543 · NIAID · DUKE UNIVERSITY · PI JOSEPH HEITMAN · 2022 to 2026
$3.6M
NIAID NIH HHS R01 AI039115NIAID NIH HHS R01 AI050113NIAID NIH HHS R01 AI170543U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01-AI050113U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01-AI170543U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01-AI39115
6 · The paper itself

Abstract

Epimutations modify gene expression and lead to phenotypic variation while the encoding DNA sequence remains unchanged. Epimutations mediated by RNA interference (RNAi) and/or chromatin modifications can confer antifungal drug resistance and may impact virulence traits in fungi. However, whether these epigenetic modifications can be transmitted across generations following sexual reproduction was unclear. This study demonstrates that RNAi epimutations conferring antifungal drug resistance are transgenerationally inherited in the human fungal pathogen Mucor circinelloides. Our research reveals that RNAi-based antifungal resistance follows a DNA sequence-independent, non-Mendelian inheritance pattern. Small RNAs (sRNAs) are the exclusive determinants of inheritance, transmitting drug resistance independently of other known repressive epigenetic modifications. Unique sRNA signature patterns can be traced through inheritance from parent to progeny, further supporting RNA as an alternative molecule for transmitting information across generations. Understanding how epimutations occur, propagate, and confer resistance may enable their detection in other eukaryotic pathogens, provide solutions for challenges posed by rising antimicrobial drug resistance, and advance research on phenotypic adaptability and its evolutionary implications.

Indexed as

Antifungal AgentsDrug Resistance, FungalEpigenesis, GeneticMucorRNA InterferenceGene Expression Regulation, FungalHumansMutationAntifungal Agents

Identifiers

PMID40775213
PMCPMC12332000

What OpenQuestion holds

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Registered trials

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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.