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形态发生和基因表达的时间动态揭示了[具体两种情况未明确]与丝状化之间的差异。

Temporal dynamics of morphogenesis and gene expression reveals distinctions between and filamentation.

作者信息

Wakade Rohan S, Wellington Melanie, Krysan Damian J

机构信息

Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.

Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.

出版信息

mSphere. 2024 Apr 23;9(4):e0011024. doi: 10.1128/msphere.00110-24. Epub 2024 Mar 19.

Abstract

is a common human fungal pathogen that is also a commensal of the oral cavity and gastrointestinal tract. pathogenesis is linked to its transition from budding yeast to filamentous morphologies including hyphae and pseudohyphae. The centrality of this virulence trait to pathobiology has resulted in extensive characterization of a wide range of factors associated with filamentation with a strong focus on transcriptional regulation. The vast majority of these experiments have used conditions to induce the yeast-to-filament transition. Taking advantage of approaches to quantitatively characterize both morphology and gene expression during filamentation during mammalian infection, we have investigated the dynamics of these two aspects of filamentation and compared them to filament induction with "host-like" tissue culture media supplemented with serum at mammalian body temperature. Although filamentation shares many common features in the two conditions, we have found two significant differences. First, alternative carbon metabolism genes are expressed early during filamentation and late , suggesting significant differences in glucose availability. Second, begins a hyphae-to-yeast transition after 4-h incubation while we find little evidence of hyphae-to-yeast transition up to 24 h post-infection. We show that the low rate of hyphae-to-yeast transition is likely due to the very low expression of , a key driver of lateral yeast and that heterologous expression of is sufficient to trigger lateral yeast formation .IMPORTANCE filamentation is correlated with virulence and is an intensively studied aspect of biology. The vast majority of studies on filamentation are based on induction of hyphae and pseudohyphae. Here we used an filamentation assay and expression profiling to compare the tempo of morphogenesis and gene expression between and filamentation. Although the hyphal gene expression profile is induced rapidly in both conditions, it remains stably expressed over a 12-h time course while it peaks after 4 h and is reduced. This reduced hyphal gene expression correlates with reduced hyphae and increased hyphae-to-yeast transition. By contrast, there is little evidence of hyphae-to-yeast transition .

摘要

是一种常见的人类真菌病原体,也是口腔和胃肠道的共生菌。其发病机制与其从出芽酵母转变为丝状形态(包括菌丝和假菌丝)有关。这种毒力特征在病理生物学中的核心地位导致了对与丝状化相关的广泛因素进行了广泛的表征,并且强烈关注转录调控。绝大多数这些实验都使用条件来诱导酵母到丝状的转变。利用方法在哺乳动物感染期间定量表征丝状化过程中的形态和基因表达,我们研究了丝状化这两个方面的动态,并将它们与在哺乳动物体温下补充血清的“宿主样”组织培养基诱导丝状化进行了比较。尽管在这两种条件下丝状化有许多共同特征,但我们发现了两个显著差异。首先,替代碳代谢基因在丝状化早期和晚期表达,这表明葡萄糖可用性存在显著差异。其次,在孵育4小时后开始从菌丝到酵母的转变,而我们发现在感染后24小时内几乎没有从菌丝到酵母转变的证据。我们表明,菌丝到酵母的低转变率可能是由于,横向酵母形成的关键驱动因素,其表达非常低,并且的异源表达足以触发横向酵母形成。重要性丝状化与毒力相关,是生物学中深入研究的一个方面。绝大多数关于丝状化的研究都是基于诱导菌丝和假菌丝。在这里,我们使用丝状化测定和表达谱分析来比较和丝状化之间形态发生和基因表达的节奏。尽管在两种条件下菌丝基因表达谱都被迅速诱导,但它在12小时的时间进程中保持稳定表达,而它在4小时后达到峰值并降低。这种降低的菌丝基因表达与减少的菌丝和增加的菌丝到酵母的转变相关。相比之下,几乎没有从菌丝到酵母转变的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8448/11036811/67473bcd4a83/msphere.00110-24.f001.jpg

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