title: Expression of UME6, a key regulator of Candida albicans hyphal development, enhances biofilm formation via Hgc1- and Sun41-dependent mechanisms.
abstract: Biofilm formation is associated with the ability of Candida 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 between C. albicans morphology and biofilm formation, we examined biofilms generated in response to expression of UME6, a key filament-specific transcriptional regulator. As UME6 levels rise, C. albicans cells are known to transition from yeast to hyphae, and we also observed a corresponding increase in the level of biofilm formation in vitro. In addition to forming a biofilm, we observed that a C. albicans strain expressing constitutive high levels of UME6 promoted 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 constitutive UME6 expression 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-level UME6 expression 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 of UME6 to induce certain filament-specific transcripts. Overall, these findings indicate a strong correlation between increased C. albicans hyphal growth and enhanced biofilm formation and also suggest functional relationships between UME6 and other regulators of biofilm development.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Mohua
authors.initials: M
authors.lastname: Banerjee
authors.forename: Priya
authors.initials: P
authors.lastname: Uppuluri
authors.forename: Xiang R
authors.initials: XR
authors.lastname: Zhao
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Carlisle
authors.forename: Geethanjali
authors.initials: G
authors.lastname: Vipulanandan
authors.forename: Cristina C
authors.initials: CC
authors.lastname: Villar
authors.forename: José L
authors.initials: JL
authors.lastname: López-Ribot
authors.forename: David
authors.initials: D
authors.lastname: Kadosh
mesh_terms: D018441:Biofilms / Q000254:growth & development*; D002176:Candida albicans / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016213:Cyclins / Q000378:metabolism*; D004847:Epithelial Cells / Q000382:microbiology; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006026:Glycoside Hydrolases / Q000378:metabolism*; D006801:Humans; D025301:Hyphae / Q000502:physiology*; D009061:Mouth Mucosa / Q000382:microbiology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D016213:Cyclins; D005656:Fungal Proteins; D014157:Transcription Factors; D006026:Glycoside Hydrolases