Abstract
Epigenetic mechanisms regulate the expression of virulence traits in diverse pathogens, including protozoan and fungi. In the human fungal pathogen Candida albicans, virulence traits such as antifungal resistance, white-opaque switching, and adhesion to lung cells are regulated by histone deacetylases (HDACs). However, the role of HDACs in the regulation of the yeast-hyphal morphogenetic transitions, a critical virulence attribute of C. albicans, remains poorly explored. In this study, we wished to determine the relevance of other HDACs on C. albicans morphogenesis. We generated mutants in the HDACs HOS1, HOS2, RPD31, and HDA1 and determined their ability to filament in response to different environmental stimuli. We found that while HOS1 and RPD31 have no or a more limited role in morphogenesis, the HDACs HOS2 and HDA1 have opposite roles in the regulation of hyphal formation. Our results demonstrate an important role for HDACs on the regulation of yeast-hyphal transitions in the human pathogen C. albicans.
Highlights
Candida albicans is the most common fungal pathogen of humans and is the fourth most common cause of nosocomial bloodstream infections [1]
Since the yeast-hyphal switch is critical for pathogenesis, we investigated the role of histone deacetylases (HDACs) in the regulation of this virulence trait
We found that HOS1 and RPD31 have little to no role in morphogenesis, and that HOS2 and HDA1 encode proteins with opposing roles in morphogenesis: Hos2 functions as a repressor, while Hda1 functions as an inducer of filamentation
Summary
Candida albicans is the most common fungal pathogen of humans and is the fourth most common cause of nosocomial bloodstream infections [1]. C. albicans pathogenesis depends on its ability to transition between the yeast, pseudophyphal, and hyphal cellular morphologies [2], and these transitions are triggered by diverse environmental cues, including temperature, serum, pH, and starvation [3]. Both the yeast and hyphal morphologies are required for pathogenesis in animal models of infection [4,5,6], and are required for the formation of normal biofilms [7,8], a structure that increases antifungal drug resistance and constitutes a source of inoculum for disseminated and recurrent infections [9]. We found that HOS1 and RPD31 have little to no role in morphogenesis, and that HOS2 and HDA1 encode proteins with opposing roles in morphogenesis: Hos functions as a repressor, while Hda functions as an inducer of filamentation
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