Mitogen activated protein kinases SakAHOG1 and MpkC collaborate for Aspergillus fumigatus virulence
Mitogen activated protein kinases SakAHOG1 and MpkC collaborate for Aspergillus fumigatus virulence
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DOI：
10.1111/mmi.13354
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发表时间：
2016-06-01
影响因子：
3.6
通讯作者：
Goldman, Gustavo H.
中科院分区：
文献类型：
--
作者：
de Oliveira Bruder Nascimento, Ariane Cristina Mendes;dos Reis, Thaila Fernanda;Goldman, Gustavo H.
本文研究了烟曲霉高渗透甘油（HOG）途径中MpkC和SakA丝裂原活化蛋白激酶对胁迫反应的影响。daka和双Delta mpkC δ sakA突变体对渗透和氧化应激以及细胞壁损伤剂更为敏感。MpkC:: GFP和SakA:: GFP在渗透胁迫和细胞壁损伤时均向细胞核转移，其中SakA:: GFP反应更快。暴露于高浓度刚果红和山梨醇后，测定了MpkA的磷酸化状态。在野生型菌株中，两种处理下MpkA磷酸化水平均逐渐升高。相反，Delta sakA突变体减少了MpkA的磷酸化，令人惊讶的是，双Delta mpkC Delta sakA没有检测到MpkA的磷酸化。烟曲霉daka和DmpkC在小鼠生存实验中毒性较强，但真菌负荷降低40%。相比之下，Delta mpkC Delta sakA双突变体表现出高度减弱的毒力，大约50%的小鼠存活，真菌负担减少75%。我们提出细胞壁完整性（CWI）和HOG途径协同作用，并且MpkC可以在暴露于几种类型的胁迫和CW生物合成过程中通过调节SakA活性起作用。
Here, we investigated which stress responses were influenced by the MpkC and SakA mitogen-activated protein kinases of the high-osmolarity glycerol (HOG) pathway in the fungal pathogen Aspergillus fumigatus. The DsakA and the double Delta mpkC Delta sakA mutants were more sensitive to osmotic and oxidative stresses, and to cell wall damaging agents. Both MpkC:: GFP and SakA:: GFP translocated to the nucleus upon osmotic stress and cell wall damage, with SakA:: GFP showing a quicker response. The phosphorylation state of MpkA was determined post exposure to high concentrations of congo red and Sorbitol. In the wild-type strain, MpkA phosphorylation levels progressively increased in both treatments. In contrast, the Delta sakA mutant had reduced MpkA phosphorylation, and surprisingly, the double Delta mpkC Delta sakA had no detectable MpkA phosphorylation. A. fumigatus DsakA and DmpkC were virulent in mouse survival experiments, but they had a 40% reduction in fungal burden. In contrast, the Delta mpkC Delta sakA double mutant showed highly attenuated virulence, with approximately 50% mice surviving and a 75% reduction in fungal burden. We propose that both cell wall integrity (CWI) and HOG pathways collaborate, and that MpkC could act by modulating SakA activity upon exposure to several types of stresses and during CW biosynthesis.