Expression ofUME6, a Key Regulator of Candida albicans Hyphal Development, Enhances Biofilm Formation via Hgc1- and Sun41-Dependent Mechanisms

Abstract

ABSTRACTBiofilm formation is associated with the ability ofCandida albicans, the major human fungal pathogen, to resist antifungal therapies and grow on tissues, catheters, and medical devices. In order to better understand the relationship betweenC. albicansmorphology and biofilm formation, we examined biofilms generated in response to expression ofUME6, a key filament-specific transcriptional regulator. AsUME6levels rise,C. albicanscells are known to transition from yeast to hyphae, and we also observed a corresponding increase in the level of biofilm formationin vitro. In addition to forming a biofilm, we observed that aC. albicansstrain expressing constitutive high levels ofUME6promoted tissue invasion in a reconstituted human three-dimensional model of oropharyngeal candidiasis. Confocal microscopy indicated that both the top and bottom layers of the biofilm generated upon high-level constitutiveUME6expression consist primarily of hyphal cells.UME6-driven biofilm formation was reduced upon deletion of Hgc1, a cyclin-related protein important for hyphal development, as well as Sun41, a putative cell wall glycosidase. Constitutive high-levelUME6expression was also able to completely bypass both the filamentation and biofilm defects of a strain deleted for Efg1, a key transcriptional regulator of these processes. Finally, we show that both Sun41 and Efg1 affect the ability ofUME6to induce certain filament-specific transcripts. Overall, these findings indicate a strong correlation between increasedC. albicanshyphal growth and enhanced biofilm formation and also suggest functional relationships betweenUME6and other regulators of biofilm development.