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HOS2 and HDA1 encode histone deacetylases with opposing roles in Candida albicans morphogenesis.

Zacchi LF, Schulz WL, Davis DA - PLoS ONE (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, University of Minnesota, Minneapolis, Minnesota, USA. zacch002@umn.edu

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.

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HDACs regulate filamentation in liquid media.Overnight YPD cultures of C. albicans wild-type (DAY185), hos2/hos2 (DAY1252), hos2/hos2 +HOS2 (DAY1250), hda1Δ/Δ (DAY1240), and hda1Δ/Δ +HDA1 (DAY1241) strains were washed in PBS, diluted 1∶100 in M199 pH 8, Spider, YP+10% BCS, and YP+0.5% GlcNAc media and incubated 3 hrs at 37°C.
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pone-0012171-g002: HDACs regulate filamentation in liquid media.Overnight YPD cultures of C. albicans wild-type (DAY185), hos2/hos2 (DAY1252), hos2/hos2 +HOS2 (DAY1250), hda1Δ/Δ (DAY1240), and hda1Δ/Δ +HDA1 (DAY1241) strains were washed in PBS, diluted 1∶100 in M199 pH 8, Spider, YP+10% BCS, and YP+0.5% GlcNAc media and incubated 3 hrs at 37°C.

Mentions: We identified Tn7::UAU1 insertion clones located close to the START codon of HOS1 (orf19.4411), HOS2 (orf19.5377), and RPD31 (orf19.6801) (Table 1). When available, two clones were used to disrupt the same gene to enhance the robustness of the approach. (Tn7::UAU1 insertions were identified within additional HDACs, but these plasmids had complex or incomplete inserts (data not shown)). We generated hos1/hos1, hos2/hos2, and rpd31/rpd31 mutants using the Tn7::UAU1 insertional mutagenesis system [24]. The hda1Δ/Δ mutant was generated by sequential gene deletion using auxotrophic markers (Table 1). All mutants were tested for filamentation in solid and liquid media (Figures 1 and 2 and Table 2). Since HOS1 and RPD31 had little effect on filamentation (data not shown), we only describe the results for the hos2/hos2 and hda1Δ/Δ mutants.


HOS2 and HDA1 encode histone deacetylases with opposing roles in Candida albicans morphogenesis.

Zacchi LF, Schulz WL, Davis DA - PLoS ONE (2010)

HDACs regulate filamentation in liquid media.Overnight YPD cultures of C. albicans wild-type (DAY185), hos2/hos2 (DAY1252), hos2/hos2 +HOS2 (DAY1250), hda1Δ/Δ (DAY1240), and hda1Δ/Δ +HDA1 (DAY1241) strains were washed in PBS, diluted 1∶100 in M199 pH 8, Spider, YP+10% BCS, and YP+0.5% GlcNAc media and incubated 3 hrs at 37°C.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2921335&req=5

pone-0012171-g002: HDACs regulate filamentation in liquid media.Overnight YPD cultures of C. albicans wild-type (DAY185), hos2/hos2 (DAY1252), hos2/hos2 +HOS2 (DAY1250), hda1Δ/Δ (DAY1240), and hda1Δ/Δ +HDA1 (DAY1241) strains were washed in PBS, diluted 1∶100 in M199 pH 8, Spider, YP+10% BCS, and YP+0.5% GlcNAc media and incubated 3 hrs at 37°C.
Mentions: We identified Tn7::UAU1 insertion clones located close to the START codon of HOS1 (orf19.4411), HOS2 (orf19.5377), and RPD31 (orf19.6801) (Table 1). When available, two clones were used to disrupt the same gene to enhance the robustness of the approach. (Tn7::UAU1 insertions were identified within additional HDACs, but these plasmids had complex or incomplete inserts (data not shown)). We generated hos1/hos1, hos2/hos2, and rpd31/rpd31 mutants using the Tn7::UAU1 insertional mutagenesis system [24]. The hda1Δ/Δ mutant was generated by sequential gene deletion using auxotrophic markers (Table 1). All mutants were tested for filamentation in solid and liquid media (Figures 1 and 2 and Table 2). Since HOS1 and RPD31 had little effect on filamentation (data not shown), we only describe the results for the hos2/hos2 and hda1Δ/Δ mutants.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, University of Minnesota, Minneapolis, Minnesota, USA. zacch002@umn.edu

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.

Show MeSH
Related in: MedlinePlus