Nitrogen availability is vital for the growth and survival of Cryptococcus neoformans in the natural environment. Two major ecological reservoirs were previously described for C. neoformans, namely, pigeon guano and the woody debris of various tree species. In contrast to the abundance of available nitrogen in guano, C. neoformans must adapt to severely limited nitrogen conditions within arboreal ecological niches. Previously, we demonstrated the role of nitrogen limitation in the production of cryptococcal virulence factors and drug tolerance. The genetic response underlying this adaptation to nitrogen deficiency, however, remains to be determined. Therefore, in the present study we investigated the transcriptomic response of C. neoformans to ecologically relevant nitrogen concentrations using RNA-sequencing. Our data revealed that low nitrogen conditions modulate the expression of numerous virulence genes in C. neoformans. Among these were, CTR4 and CGP1, which showed highly significant modulation under low nitrogen conditions. Furthermore, data analysis revealed the upregulation of antifungal tolerance-related genes in low nitrogen conditions, including genes involved in ergosterol biosynthetic processes and cell wall integrity. Overall, our findings provide insight into the survival of C. neoformans in nitrogen-poor ecological niches and suggest that pre-adaptation to these conditions may influence the pathobiology of this yeast.

中文翻译：

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新型隐球菌对生态相关氮浓度的转录组反应

氮的可用性对于新型隐球菌在自然环境中的生长和存活至关重要。先前对新型隐球菌的两个主要生态库进行了描述，即鸽粪和各种树种的木质碎片。与鸟粪中丰富的可用氮相反，新型隐球菌必须适应树栖生态位内严重受限的氮条件。以前，我们证明了氮限制在隐球菌毒力因子和药物耐受性的产生中的作用。然而，这种适应氮缺乏的遗传反应仍有待确定。因此，在本研究中，我们研究了新型隐球菌的转录组学反应使用 RNA 测序对生态相关的氮浓度进行分析。我们的数据显示，低氮条件会调节新型隐球菌中许多毒力基因的表达。其中包括 CTR4 和 CGP1，它们在低氮条件下表现出非常显着的调节作用。此外，数据分析揭示了在低氮条件下抗真菌耐受相关基因的上调，包括参与麦角甾醇生物合成过程和细胞壁完整性的基因。总体而言，我们的研究结果提供了对新型 C.neoformans在贫氮生态位中的存活的洞察，并表明对这些条件的预先适应可能会影响这种酵母的病理生物学。