Importance of a Developmentally Regulated Pheromone Receptor of Cryptococcus neoformans for Virulence

Cryptococcus neoformans is the etiologic agent of cryptococcosis. Two mating types exist in this fungus, MATα and MATa. The CPRa gene of C. neoformans is a MATa strain-specific gene and encodes a putative seven-transmembrane domain pheromone receptor. Unlike the other reported fungal pheromone receptors, CPRa shows functional diversity. Deletion of CPRa drastically affects mating efficiency but does not abolish mating. CPRa expression is developmentally regulated and is not affected by deletion of the transcriptional regulator STE12a. The expression of CPRa is markedly increased by shifting cultures from liquid to solid media. CPRa also plays a significant role in virulence. Δcpra cells produce smaller capsules in the brains of mice than the wild-type cells, and the mice infected with Δcpra survive significantly longer than those receiving the wild-type strain. Our results suggest that the MATa pheromone receptor of C. neoformans is not only required for mating but also important for survival and growth of the fungus in host tissue.