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

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Abstract
Cryptococcus neoformans is the etiologic agent of cryptococcosis. Two mating types exist in this fungus, MAT α and MAT a . The CPR a gene of C. neoformans is a MAT a strain-specific gene and encodes a putative seven-transmembrane domain pheromone receptor. Unlike the other reported fungal pheromone receptors, CPR a shows functional diversity. Deletion of CPR a drastically affects mating efficiency but does not abolish mating. CPR a expression is developmentally regulated and is not affected by deletion of the transcriptional regulator STE12 a . The expression of CPR a is markedly increased by shifting cultures from liquid to solid media. CPR a also plays a significant role in virulence. Δ cpr a cells produce smaller capsules in the brains of mice than the wild-type cells, and the mice infected with Δ cpr a survive significantly longer than those receiving the wild-type strain. Our results suggest that the MAT a pheromone receptor of C. neoformans is not only required for mating but also important for survival and growth of the fungus in host tissue.