Ergosterol Is Critical for Sporogenesis in Cryptococcus neoformans

Microbes, both bacteria and fungi, produce spores to survive stressful conditions. Spores produced by the environmental fungal pathogen Cryptococcus neoformans serve as both surviving and infectious propagules. Because of their importance in disease transmission and pathogenesis, factors necessary for cryptococcal spore germination are being actively investigated. However, little is known about nutrients critical for sporogenesis in this pathogen. Here, we found that ergosterol, the main sterol in fungal membranes, is enriched in spores relative to yeasts and hyphae. In C. neoformans, the ergosterol biosynthesis pathway (EBP) is upregulated by the transcription factor Sre1 in response to conditions that demand elevated ergosterol biosynthesis. Although the deletion of SRE1 enhances the production of mating hyphae, the sre1Δ strain is deficient at producing spores even when crossed with a wild-type partner. We found that the defect of the sre1Δ strain is specific to sporogenesis, not meiosis or basidium maturation preceding sporulation. Consistent with the idea that sporulation demands heightened ergosterol biosynthesis, EBP mutants are also defective in sporulation. We discovered that the overexpression of some EBP genes can largely rescue the sporulation defect of the sre1Δ strain. Collectively, we demonstrate that ergosterol is a critical component in cryptococcal preparation for sporulation.