The HOG MAP kinase pathway plays a crucial role in the response to different stresses in the opportunistic pathogen Candida albicans. The polyene amphotericin B (AMB) has been reported to trigger oxidative stress in several pathogenic fungi, including C. albicans. In the present work, we have analyzed the role of the MAPK Hog1 in sensing and survival to AMB treatment. Mutants lacking Hog1 are more susceptible to AMB than their parental strains and Hog1 became phosphorylated in the presence of this polyene. A set of mutated versions of Hog1 revealed that both the kinase activity and phosphorylation of Hog1 are required to cope with AMB treatment. Flow cytometry analysis showed that AMB induced intracellular ROS accumulation in both parental and hog1 null mutant strains. In addition, AMB triggered a Hog1-independent synthesis of trehalose. The addition of rotenone to AMB-treated cells improved cell viability, decreased intracellular ROS and prevented intracellular trehalose accumulation, suggesting that AMB-induced ROS is associated to a functional electron transport chain but the presence of rotenone did not impair Hog1 phosphorylation in AMB-treated cells. Our results indicate that Hog1 is necessary during AMB treatment to increase its survival.

中文翻译：

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MAPK Hog1介导了白色念珠菌对两性霉素B的反应。

HOG MAP激酶途径在机会性病原体白色念珠菌对不同压力的反应中起关键作用。据报道，多烯两性霉素B（AMB）会触发包括白念珠菌在内的几种致病真菌的氧化应激。在目前的工作中，我们分析了MAPK Hog1在AMB治疗的感觉和生存中的作用。缺少Hog1的突变体比其亲本菌株更容易受到AMB的影响，并且在存在该多烯的情况下，Hog1会被磷酸化。Hog1的一组突变版本显示，Hog1的激酶活性和磷酸化都需要应付AMB处理。流式细胞仪分析表明，AMB诱导亲本和hog1 null突变菌株中的细胞内ROS积累。此外，AMB触发了不依赖Hog1的海藻糖合成。向AMB处理的细胞中添加鱼藤酮可改善细胞活力，降低细胞内ROS并防止细胞内海藻糖积聚，这表明AMB诱导的ROS与功能性电子传输链相关，但鱼藤酮的存在并不影响AMB处理的Hog1磷酸化细胞。我们的结果表明，Hog1在AMB治疗期间必须增加其存活率。