A cyclin protein governs the infectious and sexual life cycles of Cryptococcus neoformans.

Abstract

Cell cycle is a fundamental process underlying growth and development in evolutionarily diverse organisms, including fungi. In human fungal pathogens, cell cycle control generally determines their life cycles, either in the environment or during infections. Thus, cell cycle components can potentially serve as important targets for the development of antifungal strategy against fungal infections. Here, in Cryptococcus neoformans, the most common cause of fatal fungal meningitis, we show that a previously uncharacterized B-type cyclin named Cbc1 is essential for both its infectious and sexual cycles. We reveal that Cbc1 coordinates various sexual differentiation and molecular processes, including meiosis. Especially, the absence of Cbc1 abolishes formation of sexual spores in C. neoformans, which are presumed infectious particles. Cbc1 is also required for the major Cryptococcus pathogenic attributes. Virulence assessment using the murine model of cryptococcosis revealed that the cbc1 mutant is avirulent. Together, our results provide an important insight into how C. neoformans employs shared cell cycle regulation to coordinate its infectious and sexual cycles, which are considered crucial for virulence evolution and the production of infectious spores.