Role of Rme1 in the Candida albicans virulence portfolio

Major Candida albicans virulence traits include its ability to make hyphal cells, to produce a biofilm, and to damage host cells. Former Ph.D. student Dr. Max Cravener found evidence that transcription factor gene RME1 may function as a repressor of epithelial cell damage in C. albicans: its expression levels correlated with an inverse to damage levels across multiple strains, and its overexpression blocked damage in two high-damage strains. However, a fundamental limitation of this study was the lack of rme1dd mutant phenotypes from multiple clinical strains. I pursued a new hypothesis to explain the lack of phenotype in the rme1dd mutant and how to approach it, that Rme1 may be a pathway-specific or condition-specific regulator of biofilm formation. I tested the ability of rme1d/d mutations to phenotypically suppress known hypha-defective mutations. I found that an rme1d/d mutation enables biofilm and hypha formation in brg1dd mutants, but not in efg1dd mutants. Impact of the rme1dd mutation is most prominent under biofilm-like conditions. Hypha-associated genes are significantly up-regulated in brg1dd rme1dd mutants compared to brg1dd. My results revealed that Rme1 is an interceding negative regulator under the control of Brg1 pathway in biofilm/hyphal regulatory network. These findings help resolve the paradox that Brg1, one of the most important regulators of biofilm formation, does not bind directly to most hypha-associated genes.