School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Hefei, China.
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Microbiol Spectr. 2022 Jun 29;10(3):e0265321. doi: 10.1128/spectrum.02653-21. Epub 2022 Apr 26.
Sexual reproduction facilitates infection by the production of both a lineage advantage and infectious sexual spores in the ubiquitous human fungal pathogen Cryptococcus deneoformans. However, the regulatory determinants specific for initiating mating remain poorly understood. Here, we identified a velvet family regulator, Cva1, that strongly promotes sexual reproduction in C. deneoformans. This regulation was determined to be specific, based on a comprehensive phenotypic analysis of Δ under 26 distinct and growth conditions. We further revealed that Cva1 plays a critical role in the initiation of early mating events, including sexual cell-cell fusion, but is not important for the late sexual development stages or meiosis. Thus, Cva1 specifically contributes to mating activation. Importantly, a novel mating-responsive protein, Cfs1, serves as the key target of Cva1 during mating, since its absence nearly blocks cell-cell fusion in C. deneoformans and its sister species C. neoformans. Together, our findings provide insight into how C. deneoformans ensures the regulatory specificity of mating. The human fungal pathogen C. deneoformans is a model organism for studying fungal sexual reproduction, which is considered to be important to infection. However, the specific regulatory determinants for activation of sexual reproduction remain poorly understood. In this study, by combining transcriptomic and comprehensive phenotypic analysis, we identified a velvet family regulator Cva1 that specifically and critically elicits early mating events, including sexual cell-cell fusion. Significantly, Cva1 induces mating through the novel mating-responsive protein Cfs1, which is essential for cell-cell fusion in C. deneoformans and its sister species C. neoformans. Considering that Cva1 and Cfs1 are highly conserved in species belonging to Cryptococcaeceae, they may play conserved and specific roles in the initiation of sexual reproduction in this important fungal clade, which includes multiple human fungal pathogens.
性繁殖有利于感染，因为它既能产生谱系优势，又能在无处不在的人类真菌病原体新生隐球菌中产生感染性有性孢子。然而，对于启动交配的特定调节决定因素仍知之甚少。在这里，我们鉴定了一个天鹅绒家族调节剂 Cva1，它强烈促进新生隐球菌的有性繁殖。这种调控是基于对Δ在 26 种不同的 和 生长条件下的全面表型分析来确定的。我们进一步揭示 Cva1 在早期交配事件的启动中起着关键作用，包括性细胞-细胞融合，但对后期性发育阶段或减数分裂不重要。因此，Cva1 专门促进交配激活。重要的是，一种新的交配反应蛋白 Cfs1 作为 Cva1 在交配过程中的关键靶标，因为其缺失几乎阻断了新生隐球菌和其姐妹种新生隐球菌中的细胞-细胞融合。总之，我们的研究结果提供了对新生隐球菌如何确保交配调控特异性的深入了解。人类真菌病原体新生隐球菌是研究真菌有性繁殖的模式生物，人们认为有性繁殖对感染很重要。然而，激活有性繁殖的特定调节决定因素仍知之甚少。在这项研究中，我们通过结合转录组学和全面的表型分析，鉴定了一个天鹅绒家族调节剂 Cva1，它特异性和关键地引发早期交配事件，包括性细胞-细胞融合。值得注意的是，Cva1 通过新型交配反应蛋白 Cfs1 诱导交配，Cfs1 对于新生隐球菌及其姐妹种新生隐球菌中的细胞-细胞融合是必不可少的。考虑到 Cva1 和 Cfs1 在属于隐球菌科的物种中高度保守，它们可能在这个重要的真菌类群的有性繁殖启动中发挥保守和特定的作用，该真菌类群包括多个人类真菌病原体。
