An in vitro method for inducing titan cells reveals novel features of yeast-to-titan switching in the human fungal pathogen Cryptococcus gattii.
An in vitro method for inducing titan cells reveals novel features of yeast-to-titan switching in the human fungal pathogen Cryptococcus gattii.
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DOI：
10.1371/journal.ppat.1010321
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发表时间：
2022-08
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
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隐球菌病是一种潜在的致命性真菌感染的人类引起的生物体内的新型隐球菌/gattii物种复杂。而C. neoformans是免疫功能低下个体的相对常见的病原体，C.格特氏菌能够作为免疫活性个体的主要病原体。在宿主体内，这两个物种都经历了形态发生，形成泰坦细胞：异常大的细胞，对疾病的建立至关重要。到目前为止，钛化的诱导、定义属性和潜在机制主要在C。新人类在这里，我们报告了一个偶然发现的简单和强大的协议，在体外诱导泰坦细胞在C。加提。使用这种体外方法，我们揭示了一个非常高的能力，钛内C。gattii，特别是在与太平洋西北部爆发，和Escherichia菌株的具体差异内的分支。特别是，这种方法首次证明了细胞大小的变化，DNA扩增和出芽在钛化过程中并不总是同步的。然而，有趣的是，这些细胞周期表型的表现与细胞周期进展相关的基因相关，包括CDC 11，CLN 1，BUB 2和MCM 6。最后，我们的研究结果表明，外源性对氨基苯甲酸是该生物体中钛化的关键诱导剂。因此，这种方法提供了重要的机会，为未来探索的潜在机制，钛在这一属。格特隐球菌是一种真菌病原体，可导致人类和其他动物的致命感染。进入肺后，一些（但不是全部）隐球菌细胞被诱导成为所谓的“泰坦细胞”;巨大的细胞，具有增厚的细胞壁，改变的胶囊和高度复制的DNA。作为一个关键的毒力决定因素，泰坦细胞可以操纵宿主免疫系统（避免吞噬作用和触发非保护性免疫反应），并增强向大脑的传播。到目前为止，泰坦细胞的形成过程已经在相关物种C中进行了大量研究。新人类在这里，我们描述了一种新的体外方法，以诱导泰坦细胞在C。加提。使用这种方法，我们发现了钛化过程中细胞周期表型的新的异步进展，并显示了泰坦的形成如何受到人口密度和外部环境的强烈影响;特别是分子对氨基苯甲酸的存在。
Cryptococcosis is a potentially lethal fungal infection of humans caused by organisms within the Cryptococcus neoformans/gattii species complex. Whilst C. neoformans is a relatively common pathogen of immunocompromised individuals, C. gattii is capable of acting as a primary pathogen of immunocompetent individuals. Within the host, both species undergo morphogenesis to form titan cells: exceptionally large cells that are critical for disease establishment. To date, the induction, defining attributes, and underlying mechanism of titanisation have been mainly characterized in C. neoformans. Here, we report the serendipitous discovery of a simple and robust protocol for in vitro induction of titan cells in C. gattii. Using this in vitro approach, we reveal a remarkably high capacity for titanisation within C. gattii, especially in strains associated with the Pacific Northwest Outbreak, and characterise strain-specific differences within the clade. In particular, this approach demonstrates for the first time that cell size changes, DNA amplification, and budding are not always synchronous during titanisation. Interestingly, however, exhibition of these cell cycle phenotypes was correlated with genes associated with cell cycle progression including CDC11, CLN1, BUB2, and MCM6. Finally, our findings reveal exogenous p-Aminobenzoic acid to be a key inducer of titanisation in this organism. Consequently, this approach offers significant opportunities for future exploration of the underlying mechanism of titanisation in this genus. Cryptococcus gattii is a fungal pathogen that causes lethal infections in humans and other animals. Upon entry to the lung, some (but not all) cryptococcal cells are induced to become so-called ‘titan cells’; huge cells with thickened cell walls, altered capsule and highly duplicated DNA. As a key virulence determinant, titan cells can manipulate the host immune system (avoiding phagocytosis and triggering a non-protective immune response) and enhance dissemination to the brain. Thus far, the process of forming titan cells has been largely studied in the related species C. neoformans. Here we describe a new in vitro method to induce titan cells in C. gattii. Using this approach, we discovered the novel, asynchronous progression of cell cycle phenotypes during titanisation and showed how titan formation is strongly influenced by population density as well as the external environment; in particular, the presence of the molecule p-Aminobenzoic acid.
加密型新生虫ROM2在细胞形态发生中的温度敏感作用。
影响因子：
3.7
作者：
Fuchs, Beth Burgwyn;Tang, Robin J.;Mylonakis, Eleftherios
通讯作者：
Mylonakis, Eleftherios