The HosA histone deacetylase regulates stress resistance, host cell interactions, and virulence in Aspergillus fumigatus

Hong Liu; Pamela Lee; Alice Vo; Sanjoy Paul; Quynh T Phan; Jianfeng Lin; Vincent M Bruno; Mark A Stamnes; W Scott Moye-Rowley; Scott G Filler

doi:10.1128/spectrum.04036-25

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The HosA histone deacetylase regulates stress resistance, host cell interactions, and virulence in Aspergillus fumigatus

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The HosA histone deacetylase regulates stress resistance, host cell interactions, and virulence in Aspergillus fumigatus

Hong Liu, Pamela Lee, Alice Vo, Sanjoy Paul, Quynh T Phan, Jianfeng Lin, Vincent M Bruno, Mark A Stamnes, W Scott Moye-Rowley and Scott G Filler

Microbiology spectrum, Vol.14(4), e0403625

04/2026

DOI: 10.1128/spectrum.04036-25

PMCID: PMC13055302

PMID: 41711452

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Abstract

The capacity of Aspergillus fumigatus to cause invasive pulmonary aspergillosis depends on its ability to adapt to dynamic and stressful microenvironments within the host. Epigenetic regulation, including histone deacetylation, plays a critical role in fungal adaptation to stress. Here, we investigated the role of the class I histone deacetylase HosA in A. fumigatus stress resistance, host cell interactions, and virulence. A ΔhosA mutant had increased susceptibility to intracellular oxidant stress induced by menadione. It also had impaired capacity to invade and damage two pulmonary epithelial cell lines in vitro. In a corticosteroid-immunosuppressed mouse model of invasive aspergillosis, mice infected with the ΔhosA mutant survived significantly longer than those infected with the wild-type strain, despite having similar pulmonary fungal burden. The ΔhosA mutant also induced a weaker inflammatory response than the wild-type strain. Transcriptomic analysis revealed that HosA regulates genes involved in secondary metabolite biosynthesis and energy metabolism, functioning as both an activator and repressor of distinct gene sets. Collectively, these results indicate that HosA is a key epigenetic regulator that governs A. fumigatus interactions with host cells and virulence during invasive pulmonary aspergillosis.

Aspergillus fumigatus

histone deacetylase

virulence regulation

Details

Title: Subtitle: The HosA histone deacetylase regulates stress resistance, host cell interactions, and virulence in Aspergillus fumigatus
Creators: Hong Liu - Harbor–UCLA Medical Center
Pamela Lee - Harbor–UCLA Medical Center
Alice Vo - Harbor–UCLA Medical Center
Sanjoy Paul - University of Iowa
Quynh T Phan - Harbor–UCLA Medical Center
Jianfeng Lin - Harbor–UCLA Medical Center
Vincent M Bruno - University of Maryland, Baltimore
Mark A Stamnes - University of Iowa
W Scott Moye-Rowley - University of Iowa
Scott G Filler - Harbor–UCLA Medical Center
Resource Type: Journal article
Publication Details: Microbiology spectrum, Vol.14(4), e0403625
DOI: 10.1128/spectrum.04036-25
PMID: 41711452
PMCID: PMC13055302
NLM abbreviation: Microbiol Spectr
ISSN: 2165-0497
eISSN: 2165-0497
Publisher: AMER SOC MICROBIOLOGY
Grant note: National Institute of Allergy and Infectious Diseases: 5R01AI162802
This work was supported in part by National Institutes of Health grants 5R01AI162802 to S.G.F. and W.S.M.-R., 2R01AI143198 to W.S.M.-R., and U19AI110820 to V.M.B.
Language: English
Electronic publication date: 02/19/2026
Date published: 04/2026
Academic Unit: Molecular Physiology and Biophysics; Internal Medicine
Record Identifier: 9985139486702771

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