Hagiwara Daisuke, Takahashi-Nakaguchi Azusa, Toyotome Takahito, Yoshimi Akira, Abe Keietsu, Kamei Katsuhiko, Gonoi Tohru, Kawamoto Susumu
Medical Mycology Research Center, Chiba University, Chiba, Japan.
PLoS One. 2013 Dec 2;8(12):e80881. doi: 10.1371/journal.pone.0080881. eCollection 2013.
The fungal high osmolarity glycerol (HOG) pathway is composed of a two-component system (TCS) and Hog1-type mitogen-activated protein kinase (MAPK) cascade. A group III (Nik1-type) histidine kinase plays a major role in the HOG pathway of several filamentous fungi. In this study, we characterized a group III histidine kinase, NikA/TcsC, in the life-threatening pathogenic fungus, Aspergillus fumigatus. A deletion mutant of nikA showed low conidia production, abnormal hyphae, marked sensitivity to high osmolarity stresses, and resistance to cell wall perturbing reagents such as congo red and calcofluor white, as well as to fungicides such as fludioxonil, iprodione, and pyrrolnitrin. None of these phenotypes were observed in mutants of the SskA response regulator and SakA MAPK, which were thought to be downstream components of NikA. In contrast, in response to fludioxonil treatment, NikA was implicated in the phosphorylation of SakA MAPK and the transcriptional upregulation of catA, dprA, and dprB, which are regulated under the control of SakA. We then tested the idea that not only NikA, but also the other 13 histidine kinases play certain roles in the regulation of the HOG pathway. Interestingly, the expression of fos1, phkA, phkB, fhk5, and fhk6 increased by osmotic shock or fludioxonil treatment in a SakA-dependent manner. However, deletion mutants of the histidine kinases showed no significant defects in growth under the tested conditions. Collectively, although the signal transduction network related to NikA seems complicated, NikA plays a crucial role in several aspects of A. fumigatus physiology and, to a certain extent, modulates the HOG pathway.
真菌高渗甘油（HOG）途径由双组分系统（TCS）和Hog1型丝裂原活化蛋白激酶（MAPK）级联组成。III组（Nik1型）组氨酸激酶在几种丝状真菌的HOG途径中起主要作用。在本研究中，我们对危及生命的致病真菌烟曲霉中的III组组氨酸激酶NikA/TcsC进行了表征。nikA缺失突变体表现出分生孢子产量低、菌丝异常、对高渗胁迫显著敏感，以及对刚果红和荧光增白剂等细胞壁干扰试剂以及咯菌腈、异菌脲和硝吡咯菌素等杀菌剂具有抗性。在SskA反应调节因子和SakA MAPK的突变体中未观察到这些表型，它们被认为是NikA的下游组分。相反，在咯菌腈处理后，NikA参与了SakA MAPK的磷酸化以及catA、dprA和dprB的转录上调，这些基因受SakA调控。然后我们测试了这样一种想法，即不仅NikA，而且其他13种组氨酸激酶在HOG途径的调节中也发挥一定作用。有趣的是，fos1、phkA、phkB、fhk5和fhk6的表达在渗透休克或咯菌腈处理后以SakA依赖的方式增加。然而，组氨酸激酶的缺失突变体在测试条件下的生长没有明显缺陷。总体而言，尽管与NikA相关的信号转导网络似乎很复杂，但NikA在烟曲霉生理学的几个方面发挥着关键作用，并在一定程度上调节HOG途径。
