The histone acetyltransferase GcnE regulates conidiation and biofilm formation in Aspergillus fumigatus
Abstract
Histone modifications play a crucial role in eukaryotic gene regulation. The Spt-Ada-Gcn5-acetyltransferase (SAGA) complex controls histone acetylation, with Gcn5 (GcnE) acting as the acetyltransferase. In the Aspergillus species, GcnE has been shown to regulate asexual development and secondary metabolism. Apart from this, GcnE is required for pathogenicity in plant fungal pathogen A. flavus; however, the role of GcnE in the pathogenicity of human pathogenic fungus A. fumigatus is unknown. In this study, we uncovered the key roles of GcnE in A. fumigatus conidiation, stress responses, and biofilm formation. We observed that deletion of gcnE resulted in aberrant conidiation in which conidiophores displayed abnormal phialide formation. In addition, the ΔgcnE mutant grew slightly faster under limited nitrogen sources (1 mM of ammonium or nitrate) compared to the wild type. The ΔgcnE mutant exhibited increased susceptibility to cell wall-perturbing agents, H2O2 and menadione but enhanced tolerance to LiCl. Furthermore, we showed that GcnE is involved in biofilm formation, and overexpression of adherence-related genes such as somA or uge3 partially rescued biofilm formation defects in the ΔgcnE mutant background. Interestingly, GcnE was not required for virulence in a neutropenic murine model of invasive aspergillosis. These results suggest that GcnE is critical for conidiation and biofilm formation but not virulence in A. fumigatus.
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Histone H3 post-translational modifications, such as methylation and acetylation, play a critical role in driving drug resistance and pathogenicity in human fungal pathogens.
“Recent studies have demonstrated the critical role of histone H3 PTMs, such as methylation and acetylation, in driving both drug resistance and pathogenicity in human fungal pathogens.”
From Targeting epigenetic regulators to overcome drug resistance in the emerging human fungal pathogen Candida auris (2025) · cites this paper as [28]
Disrupting the gene encoding the acetyltransferase catalytic subunit Gcn5 results in significant defects in pathogenicity and drug resistance of Candida albicans and Nakaseomyces glabratus, as well as reduced pathogenicity in Cryptococcus neoformans and multiple virulence-related phenotypes in Aspergillus fumigatus.
“Disrupting the gene encoding the acetyltransferase catalytic subunit Gcn5 results in significant defects in the pathogenicity and drug resistance of C. albicans and N. glabratus, as well as reduced pathogenicity in C. neoformans and multiple virulence-related phenotypes in A. fumigatus.”
From Targeting epigenetic regulators to overcome drug resistance in the emerging human fungal pathogen Candida auris (2025) · cites this paper as [28]
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“Forinstance,thehistoneH3 acetyltransferase complex SAGA is essential for the pathogenicity of fungi such as C. albicans , Nakaseomyces glabratus (formerly known as Candida glabrata) , C. neoformans , and A. fumigatus 25 – 28 .”
Chen, Y., Stewart, J. I. P., Liu, S., Sheppard, D. C., Lu, L., & Zhang, S. (2022) · Applied and Environmental Microbiology · doi:10.1128/aem.01535-21 · Cited by 14 · see citing works
Self-citationSong, N., Huang, Y., Zhou, X., Li, D., Liu, W., & Li, X. (2025) · Microbiology Spectrum · doi:10.1128/spectrum.02797-24
- Authors
- Lin, C.-J., Hou, Y.-H., & Chen, Y.-L.
- Affiliations
- National Taiwan University (TW)
- Corresponding author
- Chen, Ying-Lien
- Venue
- Medical Mycology
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-05-17
- Volume
- 58
- Issue
- 2
- Pages
- 248-259
- ISSN
- 0268-1218 (ISSN-L)
- 1369-3786
- 1460-2709
- OpenAlex
- W2945485160
- Cited by
- 27
- References
- 8
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 7 · 2023: 5 · 2022: 4 · 2021: 2 · 2020: 3
- FWCI
- 0.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Medical Mycology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Science and Technology (104-2320-B-002-063-MY3, 106-2923-B-002-001-MY3, 107-2320-B-002-061-MY3, 107AS-1.2.7-ST-aN)
- Council of Agriculture
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- histone acetyltransferase, Aspergillus fumigatus, conidiation, biofilm formation, SAGA complex, histone acetylation, stress tolerance, invasive aspergillosis, virulence, soma
- MeSH terms
- Invasive Fungal Infections, Animals, Aspergillus fumigatus, Female, Fungal Proteins, Mice, Inbred ICR, Mutation, Nitrogen, Spores, Fungal, Virulence, Gene Expression Regulation, Fungal, Gene Deletion, Biofilms, Mice, Histone Acetyltransferases
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