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Updated: Sep 12, 2025

Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
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RNAi epimutations conferring antifungal drug resistance are inheritable

Carlos Pérez-Arques1, María Isabel Navarro-Mendoza2,3,4, Ziyan Xu5

  • 1Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA. carlos.parq@duke.edu.

Nature Communications
|August 7, 2025
PubMed

Insights

Epimutations conferring antifungal drug resistance in fungi can be passed down through generations via small RNAs (sRNAs). This RNA-mediated inheritance is independent of DNA sequence and Mendelian genetics.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Mycology

Background:

  • Epimutations alter gene expression without changing DNA sequence, influencing traits like drug resistance.
  • RNA interference (RNAi) and chromatin modifications are known mechanisms for epimutations in fungi.
  • Transgenerational inheritance of epigenetic modifications, particularly after sexual reproduction, remained largely uncharacterized.

Purpose of the Study:

  • To investigate the transgenerational inheritance of RNAi-mediated epimutations conferring antifungal drug resistance.
  • To determine the inheritance pattern and molecular basis of this epigenetic trait in Mucor circinelloides.
  • To explore the role of small RNAs (sRNAs) in transmitting epigenetic information across generations.

Main Methods:

  • Utilized Mucor circinelloides as a model organism for studying fungal epigenetics.
  • Applied genetic and molecular techniques to track antifungal drug resistance inheritance.
  • Analyzed small RNA profiles to identify specific sRNA signatures associated with inheritance.

Main Results:

  • Demonstrated that RNAi-mediated antifungal drug resistance is transgenerationally inherited in Mucor circinelloides.
  • Established a DNA sequence-independent, non-Mendelian inheritance pattern for this trait.
  • Identified small RNAs (sRNAs) as the sole determinants responsible for transmitting drug resistance across generations.

Conclusions:

  • Small RNAs can act as carriers of epigenetic information, enabling transgenerational inheritance of acquired traits like drug resistance.
  • This RNA-based inheritance mechanism offers a new perspective on phenotypic adaptability and evolution in eukaryotic pathogens.
  • Findings have implications for understanding and combating antimicrobial drug resistance in fungal pathogens.

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