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巴西副球孢子菌(Paracoccidioides brasiliensis)中钙调蛋白的功能和遗传特征分析

Functional and genetic characterization of calmodulin from the dimorphic and pathogenic fungus Paracoccidioides brasiliensis.

作者信息

de Carvalho Maria José A, Amorim Jesuino Rosália S, Daher Bruno S, Silva-Pereira Ildinete, de Freitas Sonia M, Soares Célia M A, Felipe M Sueli S

机构信息

Lab. de Biologia Molecular, IB, Campus Universitá rio Darcy Ribeiro, Universidade de Brasília, 70910-900 Brasília-DF, Brazil.

出版信息

Fungal Genet Biol. 2003 Aug;39(3):204-10. doi: 10.1016/s1087-1845(03)00044-6.

DOI:10.1016/s1087-1845(03)00044-6
PMID:12892633
Abstract

Calmodulin (CaM) modulates intracellular calcium signalling and acts on several metabolic pathways and gene expression regulation in many eukaryotic organisms including human fungal pathogens, such as Candida albicans and Histoplasma capsulatum. The temperature-dependent dimorphic fungus Paracoccidioides brasiliensis is the aetiological agent of paracoccidioidomycosis (PCM). The mycelium (M) to yeast (Y) transition has been shown to be essential for establishment of the infection, although the precise molecular mechanisms of dimorphism in P. brasiliensis are still unknown. In this work, several inhibitory drugs of the Ca(2+)/calmodulin signalling pathway were tested to verify the role of this pathway in the cellular differentiation process of P. brasiliensis. EGTA and the drugs calmidazolium (R24571), trifluoperazine (TFP), and W7 were able to inhibit the M-Y transition. We have cloned and characterized the calmodulin gene from P. brasiliensis, which comprises 924 nucleotides and five introns that are in a conserved position among calmodulin genes.

摘要

钙调蛋白(CaM)调节细胞内钙信号传导,并作用于包括人类真菌病原体(如白色念珠菌和荚膜组织胞浆菌)在内的许多真核生物的几种代谢途径和基因表达调控。温度依赖性双态真菌巴西副球孢子菌是副球孢子菌病(PCM)的病原体。菌丝体(M)到酵母(Y)的转变已被证明对感染的建立至关重要,尽管巴西副球孢子菌双态性的确切分子机制仍然未知。在这项工作中,测试了几种Ca(2+)/钙调蛋白信号通路的抑制药物,以验证该通路在巴西副球孢子菌细胞分化过程中的作用。乙二醇双四乙酸(EGTA)以及药物氯丙咪嗪(R24571)、三氟拉嗪(TFP)和W7能够抑制M向Y的转变。我们已经克隆并鉴定了来自巴西副球孢子菌的钙调蛋白基因,该基因由924个核苷酸和五个内含子组成,这些内含子在钙调蛋白基因中处于保守位置。

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