Genetic and Phenotypic analyses of Calcineurin A subunit in Arthroderma vanbreuseghemii.
Calcineurin is a serine/threonine protein phosphatase that consists of catalytic (calcineurin A) and regulatory (calcineurin B) subunits. The conserved protein plays important roles in various biological processes. Drug combination of fluconazole and the calcineurin inhibitor (FK506) showed synergistic effects against dermatophytes. In the current study, we identified the calcineurin A homologous gene (TmcanA) in the dermatophyte Arthroderma vanbreuseghemii (anamorph: Trichophyton mentagrophytes). Knockdown mutants were produced from A. vanbreuseghemii, resulting in a defection in growth properties in accordance with dose of the suppressing reagent. The TmcanA gene restored the ability of calcineurin A-deficient Cryptococcus neoformans strain to grow at elevated temperatures. Repression of TmcanA at 37°C resulted in severely stunted growth, suggesting that this protein plays a role in tolerance to elevated temperatures. In addition, TMCANA showed an interaction with high osmolarity glycerol (HOG) signalling pathway by governing the secretion of a secondary metabolite. Moreover, expression of the hydrophobin A gene (TmHF) decreased significantly under the TmcanA-repressive condition, suggesting that TMCANA is involved in its regulation. In conclusion, calcineurin A is a multifunctional gene that is involved in the regulation of several biological processes and therefore is worth being considered as a drug target for treatment of dermatophytoses.
Laboratory of Space and Environmental Medicine, Graduate School of Medicine, Teikyo University, 2-11-1, Kaga, Itabashi, Tokyo 173-8605, Japan dr_mm_sh@hotmail.com.
Mohamed Mahdi
MM
Alshahni
Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8673, Japan.
Kiminori
K
Shimizu
Teikyo University Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo 192-0395, Japan.
Maki
M
Yoshimoto
Teikyo University Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo 192-0395, Japan.
Tsuyoshi
T
Yamada
Teikyo University Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo 192-0395, Japan.
Yayoi
Y
Nishiyama
Department of Veterinary Science, School of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonancho, Musashino, Tokyo 180-8602, Japan.
Toshiro
T
Arai
Laboratory of Space and Environmental Medicine, Graduate School of Medicine, Teikyo University, 2-11-1, Kaga, Itabashi, Tokyo 173-8605, Japan Teikyo University Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo 192-0395, Japan.
Koichi
K
Makimura
D003883:Arthrodermataceae / Q000201:enzymology* / Q000235:genetics* / Q000254:growth & development; D019703:Calcineurin / Q000235:genetics* / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D005816:Genetic Complementation Test; D013696:Temperature
D019703:Calcineurin
Hydrophobin A; calcineurin A; copper repressible promoter; dermatophytes; secondary metabolites