Divergence of TORC1-mediated stress response leads to novel acquired stress resistance in a pathogenic yeast.
Divergence of TORC1-mediated stress response leads to novel acquired stress resistance in a pathogenic yeast.
复制标题
DOI：
10.1371/journal.ppat.1011748
复制
发表时间：
2023-10
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
作者：
获得性应激抵抗（ASR）使生物体能够为初始应激源后发生的环境变化做好准备。然而，人们对 ASR 的遗传基础以及底层网络如何进化仍然知之甚少。在这项研究中，我们发现短暂的磷酸盐饥饿会诱导致病性酵母光滑酵母中的氧化应激反应（OSR）基因，并保护其免受严重的 H2O2 应激；然而，同样的治疗对低致病性的近亲酿酒酵母几乎没有什么好处。此 ASR 涉及与 OSR 相同的转录因子 (TF)，但具有不同的组合逻辑。我们发现雷帕霉素靶标复合物 1 (TORC1) 在两个物种中受到磷酸盐饥饿的差异性抑制，并通过其近端效应器 Sch9 促进 ASR。因此，磷酸盐饥饿诱导的 ASR 的进化涉及 TORC1 对磷酸盐限制的反应的重新布线，以及使用新的调控逻辑重新调整 OSR 的 TF 靶基因网络的用途。获得性应激抵抗（ASR）是一种现象，其中轻微的应激使生物体对随后的严重应激更有弹性。在这项研究中，我们发现了机会性酵母病原体光滑酵母（C. glabrata）与其致病性较低的近亲酿酒酵母（S. cerevisiae）相比具有独特的 ASR。当遭受非致命的磷酸盐饥饿时，光滑念珠菌会激活基因，增强其对严重 H2O2 应激的抵抗力，使其存活率比幼稚细胞高 3-10 倍，而相同的处理对酿酒酵母几乎没有提供保护。我们发现 ASR 的基础基因网络与典型的氧化应激反应具有相同的关键组成部分，但以不同的调控逻辑运作。值得注意的是，两个物种的雷帕霉素靶标复合物 1 (TORC1) 对磷酸盐限制的反应不同，从而支撑了 ASR 的物种差异。这一发现凸显了物种特异性的 ASR 和驱动分化的关键遗传因素。这些发现揭示了致病酵母如何适应宿主环境。
Acquired stress resistance (ASR) enables organisms to prepare for environmental changes that occur after an initial stressor. However, the genetic basis for ASR and how the underlying network evolved remain poorly understood. In this study, we discovered that a short phosphate starvation induces oxidative stress response (OSR) genes in the pathogenic yeast C. glabrata and protects it against a severe H2O2 stress; the same treatment, however, provides little benefit in the low pathogenic-potential relative, S. cerevisiae. This ASR involves the same transcription factors (TFs) as the OSR, but with different combinatorial logics. We show that Target-of-Rapamycin Complex 1 (TORC1) is differentially inhibited by phosphate starvation in the two species and contributes to the ASR via its proximal effector, Sch9. Therefore, evolution of the phosphate starvation-induced ASR involves the rewiring of TORC1’s response to phosphate limitation and the repurposing of TF-target gene networks for the OSR using new regulatory logics. Acquired Stress Resistance (ASR) is a phenomenon where mild stress makes an organism more resilient to subsequent severe stress. In this study, we uncovered a unique ASR in the opportunistic yeast pathogen C. glabrata compared to its less pathogenic relative S. cerevisiae. When subjected to a non-lethal phosphate starvation, C. glabrata activates genes that enhance its resistance to severe H2O2 stress, making it survive 3–10 times better than naïve cells, while the same treatment offers little to no protection in S. cerevisiae. We found that the underlying gene network for ASR shares key components with the typical oxidative stress response, but operates with different regulatory logics. Notably, the Target-of-Rapamycin Complex 1 (TORC1) responds differently to phosphate limitation in the two species, underpinning the species divergence in ASR. This discovery highlights a species-specific ASR and the key genetic factor driving the divergence. These findings shed light on how pathogenic yeasts adapt to their host environments.
登录
查看更多内容
影响因子：
3.4
作者：
Brunke S;Hube B
通讯作者：
Hube B
影响因子：
14.8
作者：
Gietz, R. Daniel;Schiestl, Robert H.
通讯作者：
Schiestl, Robert H.
影响因子：
3.3
作者：
Gresham, David;Boer, Viktor M.;Botstein, David
通讯作者：
Botstein, David
影响因子：
3.3
作者：
Hallett, James E. Hughes;Luo, Xiangxia;Capaldi, Andrew P.
通讯作者：
Capaldi, Andrew P.
影响因子：
--
作者：
Boisnard, Stephanie;Lagniel, Gilles;Chedin, Stephane
通讯作者：
Chedin, Stephane