A Role for Mating in Cryptococcal Virulence

This chapter discusses the effect of mating type, pheromone signaling, spore production, and ploidy on cryptococcal virulence. Cryptococcus may have the most unusual mating-type locus (MAT) of all the human-pathogenic fungi. The majority of basidiomycetous fungi have tetrapolar mating systems with two unlinked pheromone and sex-determining loci in which strains must differ at both loci for mating to succeed. In Cryptococcus, two traditional mating loci appear to have fused to generate one very large mating-type (MAT) locus that contains not only the sex-determining homeodomain transcription factors, pheromones, and pheromone receptors, but also genes from many other functional categories including several essential genes. The role of mating type in pathogenicity of C. neoformans var. grubii has been further characterized by examining the colonization of various organs by the KN99α/ α congenic strains in animal models. When infected individually, both mating types accumulate equivalently in all organs examined at early, intermediate, and late stages of the infection. While sexual recombination disrupts accumulation of deleterious mutations by reducing linkage, it can also disrupt the accumulation of beneficial mutations.