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摘要: 格特隐球菌属于新生隐球菌复合体, 既往被认为是新生隐球菌复合体的变种, 但最终被确立为独立的物种。与新生隐球菌不同, 格特隐球菌多感染免疫力正常人群, 目前致病机制尚未明确。格特隐球菌的基因组学研究不仅可全面了解其基因组成、分子进化、毒力因子以及致病机制等特点, 还可对致病相关基因和重要蛋白进行预测, 为疫苗和新型抗生素的研发提供分子基础, 并进一步为高效治疗和防控隐球菌病提供理论依据。本文就格特隐球菌的基因组测序和基本特征、基因组进化、重要毒力基因以及比较基因组研究予以概述。Abstract: Cyptococcus gattii(C.gattii) belongs to the Cryptococcus neoformans complex and was previously considered to be a variant of the Cryptococcus neoformans complex (C. neoformans var. gattii) but eventually established as a separate species. Unlike C. neoformans, C. gattii predominantly infects immunocompetent persons. The pathogenic mechanism of C. gattii is not yet clear. The genomic research of C. gattii can not only comprehensively characterize the genetic composition, molecular evolution, virulence factors and pathogenic mechanisms, but also be used for the prediction of pathogenic genes and important proteins, which further facilitates the development of vaccines and new antibiotics and the construction of new effective treatments and prevention strategies against cryptococcosis. In this paper, the whole genome sequencing, genome features, genomic evolution, important virulence factors, and comparative genomic researches are reviewed.
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Key words:
- Cyptococcus gattii /
- genome /
- comparative genome /
- evolution /
- pathogenicity
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表 1 格特隐球菌重要致病性相关基因[2]
基因 功能 表型 SOD1 细胞质抗氧化 毒力因子脲酶、磷脂酶B和漆酶的产生 SOD2 线粒体抗氧化 在37 ℃ 20%的氧气下生长 TPS1/ TPS2 海藻糖(一种抗氧化剂和压力保护剂)生物合成 交配、荚膜/黑色素的产生、细胞壁的完整性和耐热性 PKA1 信号转导通路调节子 交配、荚膜/黑色素的产生、宿主病原体相互作用 PKA2 信号转导通路调节子 交配、荚膜/黑色素的产生 PLC1 信号转导通路调节子 37 ℃下生长、黑色素/磷脂酶产生 MPK1 信号转导通路调节子 调节黑色素和荚膜产生以及细胞壁完整性 STE12ɑ 转录因子 调节黑色素产生、交配和生态适应性 GAT1 GATA转录因子 调节氮利用 CNA1 钙调素异二聚体亚基ꎬ钙调素活化的丝氨酸￣苏氨酸特异性蛋白磷酸酶 调节耐热性、质膜完整性、氟康唑耐受性和在游离钙存在下的生长 
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表 2 不同谱系格特隐球菌特异基因
谱系 基因类别 VG Ⅰ 铁还原酶样跨膜组分和铁还原酶NAD结合结构域基因 VG Ⅱ 膜转运相关的膜分泌载体膜蛋白基因、Prmt1 (Fop)染色质相关基因以及热休克蛋白70 VG Ⅲ PIF1样解旋酶和磷酸丙酮酸水合酶/烯醇酶基因 VG Ⅳ 缺失Ctr铜转运蛋白家族结构域的3个基因中的1个ꎬ以及3种卤酸脱卤素酶的Pfam结构域基因
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