Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa , Lisbon, Portugal.
iBB - Institute for Bioengineering and Biosciences, Biological Sciences Research Group, Instituto Superior Técnico , Lisboa, Portugal.
Virulence. 2020 Dec;11(1):1522-1538. doi: 10.1080/21505594.2020.1839231.
is a prominent pathogenic yeast which exhibits a unique ability to survive the harsh environment of host immune cells. In this study, we describe the role of the transcription factor encoded by the gene , here named CgTog1 after its ortholog, as a new determinant of virulence. Interestingly, Tog1 is absent in the other clinically relevant species (), being exclusive to . CgTog1 was found to be required for oxidative stress resistance and for the modulation of reactive oxygen species inside cells. Also, CgTog1 was observed to be a nuclear protein, whose activity up-regulates the expression of 147 genes and represses 112 genes in cells exposed to HO, as revealed through RNA-seq-based transcriptomics analysis. Given the importance of oxidative stress response in the resistance to host immune cells, the effect of expression in yeast survival upon phagocytosis by hemocytes was evaluated, leading to the identification of CgTog1 as a determinant of yeast survival upon phagocytosis. Interestingly, CgTog1 targets include many whose expression changes in cells after engulfment by macrophages, including those involved in reprogrammed carbon metabolism, glyoxylate cycle and fatty acid degradation. In summary, CgTog1 is a new and specific regulator of virulence in , contributing to oxidative stress resistance and survival upon phagocytosis by host immune cells.
是一种重要的致病酵母,它具有一种独特的能力,可以在宿主免疫细胞的恶劣环境中存活。在本研究中,我们描述了由基因编码的转录因子的作用,该基因在其同源物后被命名为 CgTog1,是毒力的一个新决定因素。有趣的是,Tog1 在其他临床相关的物种()中不存在,而是专属于。CgTog1 被发现对氧化应激有抗性,并且可以调节细胞内的活性氧。此外,CgTog1 被观察为一种核蛋白,其活性在细胞中上调 147 个基因的表达,并抑制 112 个基因的表达,这是通过 RNA-seq 转录组学分析揭示的。鉴于氧化应激反应在抵抗宿主免疫细胞中的重要性,评估了在被吞噬细胞吞噬后酵母中表达对酵母生存的影响,结果表明 CgTog1 是酵母在吞噬作用下生存的决定因素。有趣的是,CgTog1 的靶标包括许多在被巨噬细胞吞噬后细胞中表达变化的基因,包括那些参与重新编程的碳代谢、乙醛酸循环和脂肪酸降解的基因。总之,CgTog1 是一种新的和特定的毒力调节因子,有助于酵母对氧化应激的抗性和对宿主免疫细胞的吞噬作用的生存。