Self-Induction of a / a or α/α Biofilms in Candida albicans Is a Pheromone-Based Paracrine System Requiring Switching

Abstract

ABSTRACT Like MTL -heterozygous ( a /α) cells, white MTL -homozygous ( a / a or α/α) cells of Candida albicans , to which a minority of opaque cells of opposite mating type have been added, form thick, robust biofilms. The latter biofilms are uniquely stimulated by the pheromone released by opaque cells and are regulated by the mitogen-activated protein kinase signal transduction pathway. However, white MTL -homozygous cells, to which opaque cells of opposite mating type have not been added, form thinner biofilms. Mutant analyses reveal that these latter biofilms are self-induced. Self-induction of a / a biofilms requires expression of the α-receptor gene STE2 and the α-pheromone gene MF α, and self-induction of α/α biofilms requires expression of the a -receptor gene STE3 and the a -pheromone gene MF a . In both cases, deletion of WOR1 , the master switch gene, blocks cells in the white phenotype and biofilm formation, indicating that self-induction depends upon low frequency switching from the white to opaque phenotype. These results suggest a self-induction scenario in which minority opaque a / a cells formed by switching secrete, in a mating-type-nonspecific fashion, α-pheromone, which stimulates biofilm formation through activation of the α-pheromone receptor of majority white a / a cells. A similar scenario is suggested for a white α/α cell population, in which minority opaque α/α cells secrete a -pheromone. This represents a paracrine system in which one cell type (opaque) signals a second highly related cell type (white) to undergo a complex response, in this case the formation of a unisexual white cell biofilm.