title: NikA/TcsC histidine kinase is involved in conidiation, hyphal morphology, and responses to osmotic stress and antifungal chemicals in Aspergillus fumigatus.
abstract: 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.
authors: Medical Mycology Research Center, Chiba University, Chiba, Japan.
authors: Daisuke
authors: D
authors: Hagiwara
authors: Azusa
authors: A
authors: Takahashi-Nakaguchi
authors: Takahito
authors: T
authors: Toyotome
authors: Akira
authors: A
authors: Yoshimi
authors: Keietsu
authors: K
authors: Abe
authors: Katsuhiko
authors: K
authors: Kamei
authors: Tohru
authors: T
authors: Gonoi
authors: Susumu
authors: S
authors: Kawamoto
mesh_terms: D001232:Aspergillus fumigatus / Q000166:cytology / Q000502:physiology*; D025141:Drug Resistance, Fungal / Q000187:drug effects / Q000502:physiology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005659:Fungicides, Industrial / Q000494:pharmacology*; D017353:Gene Deletion; D005990:Glycerol / Q000494:pharmacology; D000071677:Histidine Kinase; D025301:Hyphae / Q000166:cytology / Q000201:enzymology*; D009997:Osmotic Pressure / Q000187:drug effects / Q000502:physiology*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D012997:Solvents / Q000494:pharmacology; D013172:Spores, Fungal / Q000166:cytology / Q000201:enzymology*
chemical_list: D005656:Fungal Proteins; D005659:Fungicides, Industrial; D012997:Solvents; D011494:Protein Kinases; D000071677:Histidine Kinase; D005990:Glycerol