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

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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.

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Acknowledgements

We would like to thank Dr. Guang-Jun He for critical reading and helpful suggestions. This work was financially supported by the National Science and Technology Major Project (2018ZX10101004), the Key Research Program of the Chinese Academy of Sciences (QYZDB-SSW-SSMC040), and the National Natural Science Foundation of China (31770163).

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  1. State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China

    Pengjie Hu, Linxia Liu, Weixin Ke, Xiuyun Tian & Linqi Wang

  2. University of Chinese Academy of Sciences, Beijing, 100049, China

    Pengjie Hu, Linxia Liu, Weixin Ke & Linqi Wang

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  1. Pengjie Hu
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Correspondence to Linqi Wang.

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The author(s) declare that they have no conflict of interest. The mouse experimental design and protocols used in this study were approved by the Regulation of the Institute of Microbiology, Chinese Academy of Sciences of Research Ethics Committee (permit No. SQIM-CAS007). All mouse experimental procedures were performed in accordance with the Regulations for the Administration of Affairs Concerning Experimental Animals approved by the State Council of People’s Republic of China.

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Hu, P., Liu, L., Ke, W. et al. A cyclin protein governs the infectious and sexual life cycles of Cryptococcus neoformans. Sci. China Life Sci. 64, 1336–1345 (2021). https://doi.org/10.1007/s11427-020-1697-3

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