Journal article
The HosA histone deacetylase regulates stress resistance, host cell interactions, and virulence in Aspergillus fumigatus
Microbiology spectrum, e0403625
02/19/2026
DOI: 10.1128/spectrum.04036-25
PMCID: PMC13055302
PMID: 41711452
Abstract
The capacity of
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
stress resistance, host cell interactions, and virulence. A Δ
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 a corticosteroid-immunosuppressed mouse model of invasive aspergillosis, mice infected with the Δ
mutant survived significantly longer than those infected with the wild-type strain, despite having similar pulmonary fungal burden. The Δ
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
interactions with host cells and virulence during invasive pulmonary aspergillosis.IMPORTANCEEpigenetic modifications in
can be induced by environmental changes and stresses such as those induced by interaction with host cells. HosA, a class I histone deacetylase, has been shown to play a key role in regulating secondary metabolism in several
species, but its function in
was previously unknown. We found that deletion of
increased susceptibility to intracellular, but not extracellular, oxidative stress. The Δ
mutant also exhibited significantly reduced pulmonary epithelial cell invasion and host cell damage, as well as attenuated virulence in immunosuppressed mice. Together, these findings indicate that HosA functions as a key epigenetic regulator that governs stress resistance, secondary metabolism, and fungal-host interactions. Defining the functions of HosA could provide critical insight into the epigenetic mechanisms that control fungal pathogenicity and may reveal a potential therapeutic target for invasive aspergillosis.
Details
- Title: Subtitle
- The HosA histone deacetylase regulates stress resistance, host cell interactions, and virulence in Aspergillus fumigatus
- Creators
- Hong Liu - Harbor–UCLA Medical CenterPamela Lee - Harbor–UCLA Medical CenterAlice Vo - Harbor–UCLA Medical CenterSanjoy Paul - University of IowaQuynh T Phan - Harbor–UCLA Medical CenterJianfeng Lin - Harbor–UCLA Medical CenterVincent M Bruno - University of Maryland, BaltimoreMark A Stamnes - University of IowaW Scott Moye-Rowley - University of IowaScott G Filler - Harbor–UCLA Medical Center
- Resource Type
- Journal article
- Publication Details
- Microbiology spectrum, 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
- Academic Unit
- Molecular Physiology and Biophysics; Internal Medicine
- Record Identifier
- 9985139486702771
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