Journal Article

Genetic basis for coordination of meiosis and sexual structure maturation in Cryptococcus neoformans

He, Guang-Jun, Yang, Ence, Tian, Xiuyun, Liao, Guojian, Li, Erwei, Chen, Lei, Shen, Lan, Wang, Linqi, Liu, Linxia, Zheng, Jiao, Chen, Yingying

2018

Overview

In the human fungal pathogen Cryptococcus neoformans, sex can benefit its pathogenicity through production of meiospores, which are believed to offer both physical and meiosis-created lineage advantages for its infections. Cryptococcus sporulation occurs following two parallel events, meiosis and differentiation of the basidium, the characteristic sexual structure of the basidiomycetes. However, the circuit integrating these events to ensure subsequent sporulation is unclear. Here, we show the spatiotemporal coordination of meiosis and basidial maturation by visualizing event-specific molecules in developing basidia defined by a quantitative approach. Monitoring of gene induction timing together with genetic analysis reveals co-regulation of the coordinated events by a shared regulatory program. Two RRM family regulators, Csa1 and Csa2, are crucial components that bridge meiosis and basidial maturation, further determining sporulation. We propose that the regulatory coordination of meiosis and basidial development serves as a determinant underlying the production of infectious meiospores in C. neoformans. Many microbes that cause disease form spores to survive during and between infections. These include the fungus Cryptococcus neoformans, which is the leading cause of fungal meningitis worldwide. This fungus produces spores via sexual reproduction, meaning the genes from two living strains of the fungi combine to create new lives with unique genetics. By diversifying the fungus’s genetics, sexual reproduction in Cryptococcus is considered to accelerate drug resistance. Several processes must be coordinated for Cryptococcus to reproduce sexually. Genetic information recombines through a process called meiosis, the spore-making cell (known as the sexual structure) matures and later spores are produced. Scientists have identified many genes involved in each of these processes. Yet it is not known how these processes are coordinated to ensure the proper sequence of events. Liu, He, Chen et al. studied the physical changes in Cryptococcus cells when they lost certain genes. Two genes, which the researchers named CSA1 and CSA2, were found to regulate the parallel progression of meiosis and maturation of the sexual structure. Both processes need to be complete before spore production begins. Further investigation showed that these genes are important across various strains of infectious Cryptococcus. This research highlights sexual reproduction as a target to stop Cryptococcus forming spores and starting infections. The results also show that these processes change little through evolution within a large group of fungi. The next step will be to see how these systems operate across species and the effect this has on spore production.

• Publisher: eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Analysis / Cryptococcus neoformans / Cryptococcus neoformans - cytology / Cryptococcus neoformans - genetics / Cryptococcus neoformans - growth & development / Cryptococcus neoformans - ultrastructure / Diseases / Drug resistance / Fungal infections / Fungal Proteins - genetics / Fungal Proteins - metabolism / Fungi / Gene expression / Gene Expression Regulation, Fungal / Gene Regulatory Networks / Genes / Genes, Mating Type, Fungal / Genetic analysis / Genetic aspects / Genetic research / Genomes / Health aspects / Infection / Infections / Laboratories / Maturation / Meiosis / Meiosis - genetics / Meiospores / Meningitis / Microbial drug resistance / Microbiology and Infectious Disease / Microorganisms / morphotype transition / Mutation - genetics / Pathogenicity / Phenotype / Phylogeny / Scientists / sexual reproduction / Spores, Fungal - metabolism / Sporulation / Structure (Literature) / Values