Polyploid titan cells produce haploid and aneuploid progeny to promote stress adaptation.
Polyploid titan cells produce haploid and aneuploid progeny to promote stress adaptation.
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DOI：
10.1128/mbio.01340-15
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发表时间：
2015-10-13
期刊：
影响因子：
6.4
通讯作者：
Nielsen K
中科院分区：
文献类型：
--
作者：
Gerstein AC;Fu MS;Mukaremera L;Li Z;Ormerod KL;Fraser JA;Berman J;Nielsen K
新型隐球菌是一种主要的危及生命的真菌病原体。为了应对宿主环境的压力，新生隐球菌产生大型多倍体泰坦细胞。泰坦细胞的产生增强了新型隐球菌的毒力，但泰坦细胞的多倍体方面是否特别有影响力仍然未知。我们表明，泰坦细胞更有可能在多种压力条件下生存和产生后代比典型的细胞，即使是他们正常大小的女儿保持优势，在持续暴露于压力的典型细胞。虽然多倍体泰坦细胞在营养充足的条件下，在体外复制后产生的单倍体子代细胞，泰坦细胞与抗真菌药物氟康唑治疗产生氟康唑耐药的二倍体和非整倍体的子代细胞。有趣的是，一个泰坦母细胞能够产生多种类型的非整倍体子细胞。泰坦细胞后代的存活率和基因组多样性的增加促进了对新的或高压力条件的快速适应。适应应激的能力是病原微生物在宿主中生存的关键因素，因此在发病机制中起着重要作用。在这里，我们调查了占主导地位的单倍体人类真菌病原体新型隐球菌，这是能够倍性和细胞大小增加感染过程中通过生产泰坦细胞。然后，扩大的多倍体泰坦细胞能够快速经历倍性减少以产生具有减少的倍性和/或非整倍性的后代。在应激条件下，泰坦细胞后代比典型细胞后代具有生长和存活优势。了解泰坦细胞如何在应激条件下提高隐球菌适应的速度可能有助于开发旨在阻断倍性转换的新药。
Cryptococcus neoformans is a major life-threatening fungal pathogen. In response to the stress of the host environment, C. neoformans produces large polyploid titan cells. Titan cell production enhances the virulence of C. neoformans, yet whether the polyploid aspect of titan cells is specifically influential remains unknown. We show that titan cells were more likely to survive and produce offspring under multiple stress conditions than typical cells and that even their normally sized daughters maintained an advantage over typical cells in continued exposure to stress. Although polyploid titan cells generated haploid daughter cell progeny upon in vitro replication under nutrient-replete conditions, titan cells treated with the antifungal drug fluconazole produced fluconazole-resistant diploid and aneuploid daughter cells. Interestingly, a single titan mother cell was capable of generating multiple types of aneuploid daughter cells. The increased survival and genomic diversity of titan cell progeny promote rapid adaptation to new or high-stress conditions. The ability to adapt to stress is a key element for survival of pathogenic microbes in the host and thus plays an important role in pathogenesis. Here we investigated the predominantly haploid human fungal pathogen Cryptococcus neoformans, which is capable of ploidy and cell size increases during infection through production of titan cells. The enlarged polyploid titan cells are then able to rapidly undergo ploidy reduction to generate progeny with reduced ploidy and/or aneuploidy. Under stressful conditions, titan cell progeny have a growth and survival advantage over typical cell progeny. Understanding how titan cells enhance the rate of cryptococcal adaptation under stress conditions may assist in the development of novel drugs aimed at blocking ploidy transitions.