Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, California, USA.
Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, California, USA
mSphere. 2020 Jan 15;5(1):e00672-19. doi: 10.1128/mSphere.00672-19.
is an important human pathogen responsible for causing both superficial and systemic infections. Its ability to switch from the yeast form to the hyphal growth form is required for its pathogenicity. Acidic pH inhibits hyphal initiation, but the nature of the mechanism for this inhibition is not completely clear. We show that acidic pH represses hyphal initiation independently of the temperature- and farnesol-mediated Nrg1 downregulation. Using a collection of transcription factor deletion mutants, we observed that the mutant induced hyphae in acidic pH but not in farnesol at 37°C. Furthermore, transcription of hyphal regulators and was not induced in wild-type (WT) cells but was induced in the mutant during hyphal induction in acidic pH. Using the same screening conditions with the collection of kinase mutants, we found that deletions of the core stress response mitogen-activated protein (MAP) kinase and its kinase the cell wall stress MAP kinase , and the calcium/calmodulin-dependent kinase allowed hyphal initiation in acidic pH. Furthermore, Hog1 phosphorylation induced by high osmotic stress also retarded hyphal initiation, and the effect was abolished in the and three kinase mutants but was enhanced in the phosphatase mutant We also found functional associations among Cmk1, Hog1, and Sfl1 for cation stress. Our study results suggest that robust hyphal initiation requires downregulation of both Nrg1 and Sfl1 transcriptional repressors as well as timely expression. Acidic pH and cationic stress retard hyphal initiation via the stress-responsive kinases and Sfl1. is a commensal as well as a pathogen of humans. is able to mount a cellular response to a diverse range of external stimuli in the host and switch reversibly between the yeast and hyphal growth forms. Hyphal development is a key virulence determinant. Here, we studied how senses different environmental signals to control its growth forms. Our study results suggest that robust hyphal development requires downregulation of two transcriptional repressors, Nrg1 and Sfl1. Acidic pH or cationic stress inhibits hyphal formation via stress-responsive kinases and Sfl1.
是一种重要的人类病原体，可导致浅表和全身感染。其从酵母形态切换到菌丝生长形态的能力是其致病性所必需的。酸性 pH 抑制菌丝起始，但这种抑制的机制性质尚不完全清楚。我们表明，酸性 pH 抑制菌丝起始与温度和法呢醇介导的 Nrg1 下调无关。使用转录因子缺失突变体的集合，我们观察到在酸性 pH 下，突变体诱导菌丝，但在 37°C 下的法呢醇中不诱导。此外，在野生型（WT）细胞中，菌丝调节因子和的转录没有被诱导，但在酸性 pH 下的菌丝诱导中被突变体诱导。使用相同的筛选条件，我们在激酶突变体的集合中发现，核心应激反应有丝分裂原激活蛋白（MAP）激酶和其激酶细胞壁应激 MAP 激酶的缺失，以及钙/钙调蛋白依赖性激酶允许在酸性 pH 下进行菌丝起始。此外，高渗胁迫诱导的 Hog1 磷酸化也延迟了菌丝起始，该效应在和三个激酶突变体中被消除，但在磷酸酶突变体中被增强我们还发现 Cmk1、Hog1 和 Sfl1 之间的功能关联对阳离子应激。我们的研究结果表明，强大的菌丝起始需要下调 Nrg1 和 Sfl1 转录抑制剂以及及时表达。酸性 pH 和阳离子胁迫通过应激反应激酶和 Sfl1 延迟菌丝起始。是人类的共生菌和病原体。能够对宿主中多种外部刺激做出细胞反应，并在酵母和菌丝生长形态之间可逆切换。菌丝发育是关键的毒力决定因素。在这里，我们研究了如何感知不同的环境信号来控制其生长形态。我们的研究结果表明，强大的菌丝发育需要下调两个转录抑制剂，Nrg1 和 Sfl1。酸性 pH 或阳离子胁迫通过应激反应激酶和 Sfl1 抑制菌丝形成。
