Cryptococcus neoformans is a major opportunistic fungal pathogen in AIDS and other immunosuppressed patients. We have shown that wild-type haploid C. neoformans can develop an extensive hyphal phase under appropriate conditions. Hyphae produced under these conditions are monokaryotic, possess unfused clamp connections, and develop basidia with viable basidiospores. The ability to undergo this transition is determined by the presence of the a-mating type locus and is independent of serotype. The association of the hyphal phase with the a-mating type may explain the preponderance of this mating type in the environment and the nature of the infectious propagule of C. neoformans.Since the discovery of the sexual or perfect state of the human fungal pathogen Cryptococcus neoformans by Kwon-Chung (1, 2), it has been considered a bipolar heterothallic basidiomycete with two mating types, a and a (MA Ta and MA Ta The ability of hyphae to form fruiting body-like structures in the vegetative phase is called monokaryotic, homokaryotic, or haploid fruiting (13). Although haploid fruiting is common in the higher basidiomycetes (13-15), it has not been characterized in C. neoformans, and association with mating type has never been described. Recent observations made in this laboratory and a reassessment of past studies (5, 10, 16) allow us to propose a new hypothesis for the biased mating type ratios and the nature of the infectious propagule of C. neoformans. We show here that a strains of C. neoformans can undergo a true dimorphic transition from a haploid yeast phase to a hyphal phase from which vegetative growth can continue indefinitely. The hyphal phase is induced by nitrogen starvation on a solid surface. Basidia bearing viable basidiospores are also produced, all of which are a in mating type. The ability of a but not a cells to form basidiospores under these conditions provides an attractive explanation for both the mating type bias and the nature of the infectious propagule of C. neoformans.
MATERIALS AND METHODSStrains. The strains used in this study are listed in Table 1. Auxotrophic strains were derived from JEC20 (MA Ta) and JEC21 (MA Ta). JEC20 and JEC21 are a well-characterized, haploid, congenic pair of prototrophic laboratory strains that presumably differ only at the mating type locus (17).Media
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