A negative role for master regulator Bcr1 in Candida albicans hypha-associated gene expression

Filamentation, a central virulence trait of the fungal pathogen Candida albicans, is required for host cell damage, tissue invasion, and biofilm formation. The transcription factor Bcr1 was first found to be required for biofilm formation but not filamentation. Subsequent studies revealed a negative role for Bcr1 in filamentation in opaque cells, a cell type that is required for mating, under hypoxic conditions, and in a wor2 Δ/Δ mutant background. Here we characterize a new context in which Bcr1 negatively regulates filamentation and present its associated gene expression impact. We compared the wild-type and bcr1 Δ/Δ mutant cells in the SC5314 reference strain background at 30°C in glucose media, conditions that do not induce filamentation. The bcr1 Δ/Δ mutant displayed increased invasive growth in a solid medium, and some filamentation ability in a liquid medium. The bcr1 Δ/Δ effect on filamentation was augmented by overexpression of hyphal cyclin gene HGC1, which caused pseudohyphal growth in wild-type, efg1 Δ/Δ, or brg1 Δ/Δ strains, yet caused hyphal growth in the bcr1 Δ/Δ strain. RNA-sequencing (RNA-seq) analysis of 30°C cells shows that the bcr1 Δ/Δ mutant has elevated expression of two genes that drive filamentation: HGC1 and UME6. In published data these same two genes have decreased expression in the bcr1 Δ/Δ mutant at 37°C, the temperature at which biofilm formation is typically assayed. A growing cadre of biofilm/hyphal regulators can have both positive and negative effects on hypha-associated gene expression, including Bcr1, Efg1, Ndt80, and Nrg1.

Production of filamentous cells is a central virulence trait of the fungal pathogen Candida albicans . Evidence here shows that the transcription factor Bcr1 is a negative regulator of filamentation at low temperature (30°C). Bcr1 affects expression of two drivers of filamentation, the genes HGC1 and UME6. Surprisingly, Bcr1 inhibits their expression at 30°C but stimulates their expression at 37°C. A growing number of filamentation regulators seem to function as both positive and negative regulators of filamentation, depending upon genetic and environmental contexts.