Morphotype transition and sexual reproduction are genetically associated in a ubiquitous environmental pathogen.
Morphotype transition and sexual reproduction are genetically associated in a ubiquitous environmental pathogen.
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DOI：
10.1371/journal.ppat.1004185
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发表时间：
2014-06
期刊：
影响因子：
6.7
通讯作者：
Lin X
中科院分区：
文献类型：
--
作者：
Wang L;Tian X;Gyawali R;Upadhyay S;Foyle D;Wang G;Cai JJ;Lin X
环境病原体的有性繁殖有助于最大限度地提高其谱系适应不断变化的环境和宿主。对于真菌病原体新型隐球菌，有性生殖被认为产生了超毒力和耐药性变体。该病原菌的生活史从交配开始，然后是酵母-菌丝转换和菌丝生长，最后是子实体分化和孢子形成。这些连续的分化事件是如何协调的，以确保发展的连续性是一个谜。在这里，我们揭示了遗传网络的酵母菌菌丝过渡隐球菌通过分析转录组的人口与一个同质的形态产生的工程菌株。在这个网络中，我们发现，一个Pumilio家族蛋白Pum 1和matricellular信号Cfl 1代表两个主要的平行电路指导酵母菌丝过渡。有趣的是，在α-α两性和α单性生殖过程中，只有Pum 1协调连续的形态发生事件。Pum 1启动酵母菌丝过渡，部分通过一种新的有害生物特异性分泌蛋白Fas 1; Pum 1也需要维持形态转换后的菌丝生长。此外，在实验室和临床分离物中，Pum 1指导气生菌丝随后分化成子实体。Pum 1通过调节减数分裂特异性重组酶Dmc 1的时间表达来控制有性生殖。因此，Pum 1在隐球菌交配后形态分化事件与有性生殖之间起着关键作用。我们在隐球菌中的发现说明了环境病原体如何确保其生命周期的完成，以保障其长期谱系的成功。性，尽管它的成本，是一个重要的手段，以最大限度地提高物种的适应性，在应对不可预测的环境挑战。在人类真菌病原体新型隐球菌中，有性繁殖产生了超毒力和耐药性变体，并产生空气传播的感染性孢子。在发育过程中，有性孢子是由气生菌丝分化而来的子实体产生的。隐球菌细胞通常以酵母细胞的形式生长，其亚群对交配刺激做出反应，并在交配后切换到菌丝生长。然而，连接有性生殖和多重分化事件，以确保发展的连续性的机制是未知的。在这里，我们揭示了一个网络酵母菌丝过渡隐球菌。从这个网络中，我们确定了一个Pumilio家族的RNA结合蛋白Pum 1，它与基质细胞信号Cfl 1在调节酵母到菌丝的过渡交配后的音乐会。有趣的是，Pum 1在维持菌丝生长和指导从气生菌丝形态发生到子实体形成的过程中也很重要。有趣的是，Pum 1的突变会影响花丝和减数分裂特异性蛋白Fas 1和Dmc 1的时空表达模式。我们的研究开辟了一条新的途径来研究微生物如何在保持种群异质性的同时控制发育的连续性。
Sexual reproduction in an environmental pathogen helps maximize its lineage fitness to changing environment and the host. For the fungal pathogen Cryptococcus neoformans, sexual reproduction is proposed to have yielded hyper virulent and drug resistant variants. The life cycle of this pathogen commences with mating, followed by the yeast-hypha transition and hyphal growth, and it concludes with fruiting body differentiation and sporulation. How these sequential differentiation events are orchestrated to ensure developmental continuality is enigmatic. Here we revealed the genetic network of the yeast-to-hypha transition in Cryptococcus by analyzing transcriptomes of populations with a homogeneous morphotype generated by an engineered strain. Among this network, we found that a Pumilio-family protein Pum1 and the matricellular signal Cfl1 represent two major parallel circuits directing the yeast-hypha transition. Interestingly, only Pum1 coordinates the sequential morphogenesis events during a-α bisexual and α unisexual reproduction. Pum1 initiates the yeast-to-hypha transition, partially through a novel filament-specific secretory protein Fas1; Pum1 is also required to sustain hyphal growth after the morphological switch. Furthermore, Pum1 directs subsequent differentiation of aerial hyphae into fruiting bodies in both laboratory and clinical isolates. Pum1 exerts its control on sexual reproduction partly through regulating the temporal expression of Dmc1, the meiosis-specific recombinase. Therefore, Pum1 serves a pivotal role in bridging post-mating morphological differentiation events with sexual reproduction in Cryptococcus. Our findings in Cryptococcus illustrate how an environmental pathogen can ensure the completion of its life cycle to safeguard its long-term lineage success. Sex, despite its cost, is an important means to maximize species fitness in coping with unpredictable environmental challenges. In the human fungal pathogen Cryptococcus neoformans, sexual reproduction has yielded hyper virulent and drug resistant variants, and produces airborne infectious spores. Developmentally, sexual spores are generated from fruiting bodies that are differentiated from aerial hyphae. Cryptococcus cells typically grow as yeast cells with a subpopulation that respond to mating stimulation and switch to hyphal growth after mating. However, mechanisms that connect sexual reproduction and multiple differentiation events to ensure the developmental continuality are unknown. Here we revealed a network of yeast-to-hypha transition in Cryptococcus. From this network we identified a Pumilio-family RNA binding protein Pum1 that acts in concert with the matricellular signal Cfl1 in regulating the yeast-to-hyphal transition following mating. Interestingly, Pum1 is also important in sustaining hyphal growth and in directing the progression from aerial hyphal morphogenesis to the formation of fruiting bodies. Intriguingly, mutations of Pum1 affect the spatiotemporal expression pattern of the filament- and meiosis-specific proteins Fas1 and Dmc1. Our study opens a new avenue to investigate how a microbe controls development continuity while maintaining population heterogeneity.
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3.1
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