Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, E-28040, Madrid, Spain.
Área de Microbiología, Facultad de Biología, Universidad de Murcia, E-30071, Murcia, Spain.
Microbiol Res. 2017 Oct;203:10-18. doi: 10.1016/j.micres.2017.06.004. Epub 2017 Jun 17.
Arsenic is a toxic metalloid widespread in nature. Recently, it has been demonstrated a main role of the transcription factor Pho4 in the acquisition of tolerance to arsenic-derived compounds, arsenite and arsenate in Candida albicans. Here, the effect of these compounds on this pathogenic yeast has been analyzed. In wild type cells, both arsenite and arsenate induced a marked increase in the endogenous production of Reactive Oxygen Species (ROS), together with the accumulation of intracellular trehalose and the activation of catalase, suggesting their role as generators of oxidative stress in this yeast. However, a pho4 null mutant showed a minor increase of intracellular ROS and a different kinetics of catalase activation upon exposure to arsenite and arsenate. Interestingly, the enzymatic activity of glutathione reductase and superoxide dismutase were exclusively triggered by arsenite but not by arsenate. pho4 mutant cells were also found to be sensitive to azide but significantly resistant to arsenate through a process dependent on an active electron transport chain and the alternative oxidase system. Therefore, arsenic-derived compounds induce a strong antioxidant response in C.albicans via different mechanisms.
砷是一种广泛存在于自然界中的有毒类金属。最近，研究表明转录因子 Pho4 在获得耐砷化合物（亚砷酸盐和砷酸盐）方面发挥着主要作用，这种化合物存在于白色念珠菌中。本文分析了这些化合物对这种致病性酵母的影响。在野生型细胞中，亚砷酸盐和砷酸盐均会导致内源性活性氧（ROS）的产生显著增加，同时细胞内海藻糖的积累和过氧化氢酶的激活，表明它们在该酵母中作为氧化应激的发生剂。然而， pho4 缺失突变体在接触亚砷酸盐和砷酸盐时，细胞内 ROS 的增加较少，过氧化氢酶的激活动力学也不同。有趣的是，谷胱甘肽还原酶和超氧化物歧化酶的酶活性仅被亚砷酸盐触发，而不受砷酸盐触发。 pho4 突变体细胞对叠氮化物敏感，但对砷酸盐高度敏感，这一过程依赖于活跃的电子传递链和替代氧化酶系统。因此，砷化合物通过不同的机制在白色念珠菌中诱导强烈的抗氧化反应。
