The role of Candida albicans FAR1 in regulation of pheromone-mediated mating, gene expression and cell cycle arrest

Candida albicans cells homozygous for the MTLa locus respond to alpha-mating pheromone by activating gene expression and triggering morphological changes, and the cells undergo a pheromone-mediated cell cycle arrest that can be influenced by nutritional conditions. Disruption of C. albicans ORF19.7105, which is the predicted homologue of the yeast FAR1 gene, blocks pheromone-mediated morphological changes, prevents pheromone-mediated cell cycle arrest, greatly compromises mating and also blocks pheromone-triggered gene induction. C. albicans ORF19.7105 is not pheromone inducible, but overexpression of this gene from the actin promoter greatly enhances pheromone-mediated cell cycle arrest, leading to clear halos in growth inhibition assays on a variety of solid media. Transcriptional profiling of the ORF19.7105-overexpressing strain has established an enhanced responsiveness of pheromone-induced genes. Thus the C. albicans FAR1 gene is a dosage-dependent regulator of the pheromone response, and is critically required for all aspects of mating process of this pathogenic fungus.