The Fungicidal Action of Micafungin is Independent on Both Oxidative Stress Generation and HOG Pathway Signaling in Candida albicans.
The Fungicidal Action of Micafungin is Independent on Both Oxidative Stress Generation and HOG Pathway Signaling in Candida albicans.
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DOI：
10.3390/microorganisms8121867
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发表时间：
2020-11-26
期刊：
影响因子：
4.5
通讯作者：
Argüelles JC
中科院分区：
文献类型：
--
作者：
Alonso-Monge R;Guirao-Abad JP;Sánchez-Fresneda R;Pla J;Yagüe G;Argüelles JC
在真菌中，丝裂原活化蛋白激酶（MAPK）途径感知各种各样的环境刺激，导致细胞适应和存活。HOG通路在白色念珠菌的病理生物学中起着重要作用，包括小鼠模型中胃肠道的定殖、毒力和对应激的反应。在这里，我们研究了Hog 1在C.白色念珠菌对临床相关的抗真菌剂米卡芬净（MF）的反应，其最低抑菌浓度（MIC）在亲本菌株（RM 100）和同基因纯合突变体hog 1（0.016 mg/L）中相同。细胞活力受损的亲本菌株，同基因hog 1突变体，和Hog 1 + reintegrant之间没有显着差异。这种表型与在不同的C.白色背景。MF处理的细胞未能诱导相关增加的活性氧（ROS）的形成和激活的线粒体膜电位在父母和hog 1细胞。MF也不能触发编码抗氧化活性过氧化氢酶（CAT 1）和超氧化物歧化酶（SOD 2）的基因的任何显著激活，以及相应的酶活性，而在两性霉素B（AMB）的存在下观察到明显的诱导，作为Hog 1信号传导的阳性对照。此外，Hog 1没有磷酸化的MF的加入，但值得注意的是，这种棘白菌素引起Mkc 1磷酸化。我们的研究结果强烈提示MF对C.白色念珠菌细胞的Hog 1 MAPK不介导的，是独立的产生内部氧化应激的C。白色念珠菌。
In fungi, the Mitogen-Activated Protein kinase (MAPK) pathways sense a wide variety of environmental stimuli, leading to cell adaptation and survival. The HOG pathway plays an essential role in the pathobiology of Candida albicans, including the colonization of the gastrointestinal tract in a mouse model, virulence, and response to stress. Here, we examined the role of Hog1 in the C. albicans response to the clinically relevant antifungal Micafungin (MF), whose minimum inhibitory concentration (MIC) was identical in the parental strain (RM100) and in the isogenic homozygous mutant hog1 (0.016 mg/L). The cell viability was impaired without significant differences between the parental strain, the isogenic hog1 mutant, and the Hog1+ reintegrant. This phenotype was quite similar in a collection of hog1 mutants constructed in a different C. albicans background. MF-treated cells failed to induce a relevant increase of both reactive oxygen species (ROS) formation and activation of the mitochondrial membrane potential in parental and hog1 cells. MF was also unable to trigger any significant activation of the genes coding for the antioxidant activities catalase (CAT1) and superoxide dismutase (SOD2), as well as on the corresponding enzymatic activities, whereas a clear induction was observed in the presence of Amphotericin B (AMB), introduced as a positive control of Hog1 signaling. Furthermore, Hog1 was not phosphorylated by the addition of MF, but, notably, this echinocandin caused Mkc1 phosphorylation. Our results strongly suggest that the toxic effect of MF on C. albicans cells is not mediated by the Hog1 MAPK and is independent of the generation of an internal oxidative stress in C. albicans.
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影响因子：
11.8
作者：
Pappas, Peter G.;Rotstein, Coleman M. F.;Buell, Donald N.
通讯作者：
Buell, Donald N.
影响因子：
2.8
作者：
Arana, DM;Nombela, C;Pla, J
通讯作者：
Pla, J
影响因子：
4.1
作者：
Guirao-Abad, Jose P.;Sanchez-Fresneda, Ruth;Arguelles, Juan-Carlos
通讯作者：
Arguelles, Juan-Carlos
影响因子：
2.8
作者：
Navarro-García, F;Eisman, B;Pla, J
通讯作者：
Pla, J
影响因子：
158.5
作者：
Mora-Duarte, J;Betts, R;Perfect, J
通讯作者：
Perfect, J