Negative control of Candida albicans biofilm formation by combined action of white-opaque regulator Wor2 and biofilm regulator Bcr1.

Biofilm formation is vital for the survival and pathogenicity of the fungus Candida albicans. Expression of biofilm-promoting genes is coordinated by a transcription factor network that governs the yeast-filament transition and other processes. A second cell type transition, the white-opaque transition, is coordinated by its own transcription factor network. Initial studies suggested that the 2 transcriptional networks have a mutually exclusive relationship, driven in part by reciprocal repression of biofilm regulator Efg1 and white-opaque regulator Wor1. However, recent studies have shown that biofilm regulators and white-opaque regulators can promote one another's function in many situations. Here, we test the function of white-opaque regulator Wor2 in biofilm formation. We find that Wor2 has a functional relationship with biofilm regulator Bcr1. We characterized the phenotype of bcr1Δ/Δ wor2Δ/Δ mutants in 5 strain backgrounds and conducted RNA-sequencing (RNA-seq) analysis in the SC5314 reference strain background. The combined Bcr1-Wor2 impact is unexpected: although Bcr1 is known as a positive regulator of biofilm formation and biofilm-related genes, the bcr1Δ/Δ wor2Δ/Δ mutants have increased biofilm or filamentation capacity, depending on the strain, and increased expression of biofilm-related genes. Those properties suggest that Wor2 and Bcr1 function together as negative regulators of biofilm formation. Our findings argue that Bcr1 can act as both a positive and negative regulator of downstream effector genes in the biofilm network and establish a new connection between the biofilm and white-opaque regulatory networks.