The histone deubiquitinase Ubp10 modulates stress response, drug resistance, and virulence in Candida glabrata
Journal
Medical Mycology
Journal Volume
64
Journal Issue
1
ISSN
1369-3786
Date Issued
2026-01
Author(s)
Abstract
Candida glabrata has emerged as a leading cause of fungal infections worldwide, characterized by inherent antifungal resistance. While considerable attention has focused on conventional resistance mechanisms, the contribution of epigenetic regulation to C. glabrata pathogenicity remains incompletely understood. Here, we investigated the role of Ubp10, a histone H2B deubiquitinase, in C. glabrata stress adaptation and virulence. Deletion of UBP10 resulted in a substantial increase in H2B ubiquitination compared to the wild-type, indicating its predominant role in H2B deubiquitination. Phenotypic characterization revealed that ubp10 mutant exhibited impaired growth kinetics, mitochondrial dysfunction with elevated reactive oxygen species production, and altered morphogenetic responses, including enhanced agar invasion but reduced biofilm formation. Most notably, the ubp10 mutant displayed a distinctive antifungal susceptibility profile with increased resistance to azoles coupled with enhanced susceptibility to echinocandins, correlating with dysregulated expression of drug-response genes (ERG6, ERG11, CDR1, FKS1, and FKS2). Transcriptional analysis further demonstrated that key oxidative stress response genes (CTA1, SOD1, and GPX2) were downregulated under basal conditions but hyperactivated upon H₂O₂ exposure. In a murine model of systemic candidiasis, the ubp10 mutant was avirulent, with 100% host survival. These findings establish Ubp10 as an important epigenetic regulator involved in C. glabrata pathobiology, linking histone H2B deubiquitination to stress adaptation, drug resistance, and virulence phenotypes.
Subjects
antifungal resistance
Candida glabrata
epigenetic regulation
histone deubiquitination
Ubp10
virulence
Publisher
Oxford University Press (OUP)
Description
Article number myaf126.
Type
journal article