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

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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

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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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Authors: Chang, Z., & Heitman, J.
Affiliations: Duke University (US)
Corresponding author: Heitman, Joseph
ORCID: Chang, Zanetta
Heitman, Joseph
Venue: mBio
Publisher: American Society for Microbiology
Published: 2019-12-24
Volume: 10
Issue: 6
ISSN: 2150-7511 (ISSN-L)
2161-2129
DOI: 10.1128/mbio.02579-19
PMC: PMC6831780
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: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
journals.asm.org/non-commercial-tdm-license (tdm)
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 › Infectious Diseases › 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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Drug-Resistant Epimutants Exhibit Organ-Specific Stability and Induction during Murine Infections Caused by the Human Fungal Pathogen Mucor circinelloides

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