Candida albicans can stochastically switch between two phenotypes, white and opaque. Opaque cells are the sexually competent form of C. albicans and therefore undergo efficient polarized growth and mating in the presence of pheromone. In contrast, white cells cannot mate, but are induced – under a specialized set of conditions – to form biofilms in response to pheromone. In this work, we compare the genetic regulation of such “pheromone-stimulated” biofilms with that of “conventional” C. albicans biofilms. In particular, we examined a network of six transcriptional regulators (Bcr1, Brg1, Efg1, Tec1, Ndt80, and Rob1) that mediate conventional biofilm formation for their potential roles in pheromone-stimulated biofilm formation. We show that four of the six transcription factors (Bcr1, Brg1, Rob1, and Tec1) promote formation of both conventional and pheromone-stimulated biofilms, indicating they play general roles in cell cohesion and biofilm development. In addition, we identify the master transcriptional regulator of pheromone-stimulated biofilms as C. albicans Cph1, ortholog of Saccharomyces cerevisiae Ste12. Cph1 regulates mating in C. albicans opaque cells, and here we show that Cph1 is also essential for pheromone-stimulated biofilm formation in white cells. In contrast, Cph1 is dispensable for the formation of conventional biofilms. The regulation of pheromone- stimulated biofilm formation was further investigated by transcriptional profiling and genetic analyses. These studies identified 196 genes that are induced by pheromone signaling during biofilm formation. One of these genes, HGC1, is shown to be required for both conventional and pheromone-stimulated biofilm formation. Taken together, these observations compare and contrast the regulation of conventional and pheromone-stimulated biofilm formation in C. albicans, and demonstrate that Cph1 is required for the latter, but not the former.
Candida albicans is the predominant fungal pathogen afflicting humans, where many infections arise due to its proclivity to form biofilms. Biofilms are complex multicellular communities in which cells exhibit distinct properties to those grown in suspension. They are particularly relevant in the development of device-associated infections, and thus understanding biofilm regulation and biofilm architecture is a priority. C. albicans has the ability to form different types of biofilms under different environmental conditions. Here, we compare the regulation of biofilm formation in conventional biofilms, for which a core transcriptional network has recently been identified, with pheromone-stimulated biofilms, which occur when C. albicans white cells are exposed to pheromone. Our studies show that several regulatory components control biofilm formation under both conditions, including the network transcriptional regulators Bcr1, Brg1, Rob1, and Tec1. However, other transcriptional regulators are specific to each model of biofilm development. In particular, we demonstrate that Cph1, the master regulator of the pheromone response during mating, is essential for pheromone-stimulated biofilm formation but is dispensable for conventional biofilms. These studies provide an in-depth analysis of the regulation of pheromone-stimulated biofilms, and demonstrate that both shared and unique components operate in different models of biofilm formation in this human pathogen.