Cited by 205Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Infections and Studies

Drug-Resistant Epimutants Exhibit Organ-Specific Stability and Induction during Murine Infections Caused by the Human Fungal Pathogen Mucor circinelloides

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Chang, Zanetta, Heitman, Joseph·2019·mBio

Published version of a preprint

Abstract

The emerging fungal pathogen Mucor circinelloides causes a severe infection, mucormycosis, which leads to considerable morbidity and mortality. Treatment of Mucor infection is challenging because Mucor is inherently resistant to nearly all clinical antifungal agents. An RNAi-dependent and reversible mechanism of antifungal resistance, epimutation, was recently reported for Mucor . Epimutation has not been studied in vivo , and it was unclear whether it would contribute to antifungal resistance observed clinically. We demonstrate that epimutation can both be induced and reverted after in vivo passage through a mouse; rates of both induction and reversion are higher after brain infection than after infection of other organs (liver, spleen, kidneys, or lungs). Elucidating the roles played by epimutation in drug resistance and infection will improve our understanding of Mucor and other fungal pathogens and may have implications for antifungal treatment.

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  • Epimutation-mediated drug resistance represents a potential clinically-relevant factor affecting drug resistance.

    “In a systemic mouse model of Mucor infection, epimutation-mediated drug resistance can be rapidly induced and reverted over the course of the infection, and thus represents a potential clinically-relevant factor affecting drug resistance103.”

    From Molecular mechanisms governing antifungal drug resistance (2023) · cites this paper as [103]

  • In a systemic mouse model of Mucor infection, epimutation-mediated drug resistance can be rapidly induced and reverted over the course of the infection.

    “In a systemic mouse model of Mucor infection, epimutation-mediated drug resistance can be rapidly induced and reverted over the course of the infection, and thus represents a potential clinically-relevant factor affecting drug resistance103.”

    From Molecular mechanisms governing antifungal drug resistance (2023) · cites this paper as [103]

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Authors
Chang, Z., & Heitman, J.
Affiliations
Duke University (US)
Corresponding author
Heitman, Joseph
Venue
mBio
Published
2019-12-24
Volume
10
Issue
6
ISSN
  • 2150-7511 (ISSN-L)
  • 2161-2129
OpenAlex
W2985567791
Cited by
202
References
43
Citations by year
2026: 21 · 2025: 16 · 2024: 22 · 2023: 30 · 2022: 42 · 2021: 39 · 2020: 30 · 2019: 2
FWCI
21.85
Type
journal article
Language
en
Open access
Locations
  • mBio (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
HHS | National Institutes of Health (AI39115-21, AI50113-15, AI104533-05, AI112595-04)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Keywords
Mucor circinelloides, mucormycosis, epimutations, antifungal resistance, brain infection, fungal pathogens
MeSH terms
Animals, Antifungal Agents, Disease Models, Animal, Humans, Male, Mice, Inbred BALB C, Mucor, Mucormycosis, Tacrolimus, Sirolimus, Drug Resistance, Fungal, RNA Interference, Epigenesis, Genetic, Mice

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