Abstract
To mate, MTL-homozygous strains of the yeast pathogen Candida albicans must switch from the white to opaque phase. Mating-competent opaque cells then release pheromone that induces polarization, a G1 block and conjugation tube formation in opaque cells of opposite mating type. Pheromone also induces mating-incompetent white cells to become adhesive and cohesive, and form thicker biofilms that facilitate mating. The pheromone response pathway of white cells shares the upstream components of that of opaque cells, but targets a different transcription factor. Here we demonstrate that the genes up-regulated by the pheromone in white cells are activated through a common cis-acting sequence, WPRE, which is distinct from the cis-acting sequence, OPRE, responsible for up-regulation in opaque cells. Furthermore, we find that these white-specific genes play roles in white cell biofilm formation, and are essential for biofilm formation in the absence of an added source of pheromone, suggesting either an autocrine or pheromone-independent mechanism. These results suggest an intimate, complex and unique relationship between switching, mating and MTL-homozygous white cell biofilm formation, the latter a presumed virulence factor in C. albicans.
Highlights
In nature, the majority of natural strains of Candida albicans are heterozygous (a/a) at the mating type locus, MTL [1,2,3,4]
C. albicans forms two types of biofilm, one by cells of majority strains that are heterozygous at the mating type locus, and another by white cells of minority strains that are homozygous at the mating type locus
The white cell biofilm response to pheromone is regulated by a pheromone response pathway that shares all of the upper components of the opaque cell mating response pathway, but targets a different transcription factor and activates different phase-specific downstream genes
Summary
The majority of natural strains of Candida albicans are heterozygous (a/a) at the mating type locus, MTL [1,2,3,4]. To mate, they must first undergo homozygosis to a/a or a/a [5,6,7], switch from the white to unique opaque phenotype [8,9]. In the case of biofilms formed by C. albicans white cells, it provides an environment that facilitates mating [20]. The white cell response to pheromone has been shown to be a general characteristic of MTL-homozygous strains for all of the major clades of C. albicans, including derivatives of the laboratory strain SC5314 [24]
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