Role of Cln1 during melanization of Cryptococcus neoformans.
Role of Cln1 during melanization of Cryptococcus neoformans.
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DOI：
10.3389/fmicb.2015.00798
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发表时间：
2015
影响因子：
5.2
通讯作者：
Zaragoza O
中科院分区：
文献类型：
--
作者：
García-Rodas R;Trevijano-Contador N;Román E;Janbon G;Moyrand F;Pla J;Casadevall A;Zaragoza O
新型隐球菌是一种机会性真菌病原体，具有几种描述良好的毒力决定因素。其中最重要的是多糖胶囊和产生黑色素的能力。黑化既发生在体外，在儿茶酚胺和吲哚化合物的存在下，也发生在体内感染期间。尽管黑色素的产生对隐球菌的毒力很重要，但其合成的成分和机制尚未完全阐明。在这项工作中，我们描述了G1/S周期蛋白（Cln1）在黑色素化过程中的作用。Cln1特异地进化出仅存在于其他担子菌中的蛋白质。我们发现Cln1是新生巨噬细胞细胞壁稳定和黑色素生成所必需的。黑色素化的缺失与LAC1基因表达缺陷相关。细胞周期元件与黑色素化之间的关系被药物的作用所证实，这些药物导致细胞周期在特定阶段停滞，如雷帕霉素。在诱导黑化的培养基中，cln1突变体始终更容易受到氧化损伤。我们的研究结果强烈表明，新生C. Cln1在毒力性状的表达中具有一种新的、迄今为止未被认识到的作用。
Cryptococcus neoformans is an opportunistic fungal pathogen that has several well-described virulence determinants. A polysaccharide capsule and the ability to produce melanin are among the most important. Melanization occurs both in vitro, in the presence of catecholamine and indole compounds, and in vivo during the infection. Despite the importance of melanin production for cryptococcal virulence, the component and mechanisms involved in its synthesis have not been fully elucidated. In this work, we describe the role of a G1/S cyclin (Cln1) in the melanization process. Cln1 has evolved specifically with proteins present only in other basidiomycetes. We found that Cln1 is required for the cell wall stability and production of melanin in C. neoformans. Absence of melanization correlated with a defect in the expression of the LAC1 gene. The relation between cell cycle elements and melanization was confirmed by the effect of drugs that cause cell cycle arrest at a specific phase, such as rapamycin. The cln1 mutant was consistently more susceptible to oxidative damage in a medium that induces melanization. Our results strongly suggest a novel and hitherto unrecognized role for C. neoformans Cln1 in the expression of virulence traits.