The high-osmolarity glycerol (HOG) response pathway is a multifunctional signal transduction pathway that specifically transmits ambient osmotic signals. Saccharomyces cerevisiae Hog1p has two upstream signaling branches, the sensor histidine kinase Sln1p and the receptor Sho1p. The Sho1p branch includes two other proteins, the Msb2p mucin and Opy2p. Aspergillus fumigatus is the leading cause of pulmonary fungal diseases. Here, we investigated the roles played by A. fumigatus SlnA^Sln1p, ShoA^Sho1p, MsbA^Msb2p, and OpyA^Opy2p putative homologues during the activation of the mitogen-activated protein kinase (MAPK) HOG pathway. The shoA, msbA, and opyA singly and doubly null mutants are important for the cell wall integrity (CWI) pathway, oxidative stress, and virulence as assessed by a Galleria mellonella model. Genetic interactions of ShoA, MsbA, and OpyA are also important for proper activation of the SakA^Hog1p and MpkA^Slt2 cascade and the response to osmotic and cell wall stresses. Comparative label-free quantitative proteomics analysis of the singly null mutants with the wild-type strain upon caspofungin exposure indicates that the absence of ShoA, MsbA, and OpyA affects the osmotic stress response, carbohydrate metabolism, and protein degradation. The putative receptor mutants showed altered trehalose and glycogen accumulation, suggesting a role for ShoA, MsbA, and OpyA in sugar storage. Protein kinase A activity was also decreased in these mutants. We also observed genetic interactions between SlnA, ShoA, MsbA, and OpyA, suggesting that both branches are important for activation of the HOG/CWI pathways. Our results help in the understanding of the activation and modulation of the HOG and CWI pathways in this important fungal pathogen.

中文翻译：

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在烟曲霉适应不同压力源和碳源期间，假定的膜受体有助于丝裂原活化蛋白激酶级联的激活和有效信号传递。

高渗透压甘油 (HOG) 反应通路是一种多功能信号转导通路，专门传递环境渗透信号。酿酒酵母Hog1p 有两个上游信号分支，传感器组氨酸激酶 Sln1p 和受体 Sho1p。Sho1p 分支包括另外两种蛋白质，Msb2p 粘蛋白和 Opy2p。烟曲霉是导致肺部真菌病的主要原因。在这里，我们研究了烟曲霉SlnA ^Sln1p、ShoA ^Sho1p、MsbA ^Msb2p和 OpyA ^Opy2p推定同源物在丝裂原活化蛋白激酶 (MAPK) HOG 通路激活过程中所起的作用。该绍阿、msbA和opyA单和双无效突变体对细胞壁完整性 (CWI) 途径、氧化应激和毒力很重要，正如大蜡螟模型所评估的那样。的SHO A，MSBA和OpyA的遗传相互作用也是萨卡的正确激活重要^Hog1p和MpkA ^SLT2级联反应以及对渗透压和细胞壁应力的反应。卡泊芬净暴露后野生型菌株的单空突变体的无标记定量蛋白质组学比较分析表明，ShoA、MsbA 和 OpyA 的缺失会影响渗透应激反应、碳水化合物代谢和蛋白质降解。假定的受体突变体显示出海藻糖和糖原积累的改变，表明 ShoA、MsbA 和 OpyA 在糖储存中的作用。这些突变体的蛋白激酶 A 活性也降低。我们还观察到 SlnA、ShoA、MsbA 和 OpyA 之间的遗传相互作用，表明这两个分支对于 HOG/CWI 通路的激活都很重要。我们的结果有助于了解这一重要真菌病原体中 HOG 和 CWI 通路的激活和调节。