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Molecular Mechanism of Cell Cycle Regulation of Pathogenic Fungi Cryptococcus neoformans

病原真菌新型隐球菌细胞周期调控的分子机制

基本信息

批准号：
17590386
负责人：
KAWAMOTO Susumu
金额：
$ 2.37万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590386/
关键词：
Fungi Infectious disease Cell cycle Gene Protein Cryptococcus Cyclin Cyclin-dependent kinase

项目摘要

Cryptococcus neoformans is an opportunistic pathogen, belongs to basidiomycetous fungus, and has unique properties in cell cycle progression. In standard liquid condition, doubling time of exponentially growing C. neoformans was 132+-16 min, and duration time of G1, S, G2, and M phases were found to be about 71, 18, 25, and 18 min, respectively. DNA synthesis started before bud emergence, and completed by the stage that the size of bud became 1/4 of the mother cell. The doubling time of daughter cells was about twice as that of the mother cells. The spindle pole body was located on the outer nuclear envelop and showed duplicated form in G1 to G2 phase. Cyclin-dependent kinase (Ddk) has been known to control cell cycle by changing conformation and biological functions. Cdk has been also known to bind to or separate from the molecules, expecially cyclins, and to change substrate specificity of the enzyme. In C.neoformans, Cdk and cyclins were cloned by ourselves, and protein-protein interaction profile between the two proteins were analyzed and constructed in silico. We are further analyzing structure-function relationship between C. neoformans Cdk and cyclins.C. neoformans is killed by the bacterium Staphylococcus aureus and this death is inhibited by soluble capsular polysaccharides. To investigate the mechanism of killing, cells in co-culture were examined under scanning and transmission electron microscopy. S. aureus attached to the capsule of C. neoformans, and the ultrastructure of the attached C. neoformans cells was characteristic of dead cells. We identified the molecules that contributed to the fungal-bacterial interaction : triosephosphate isomerase (TPI) on S. aureus adheres to the capsule of C. neoformans by recognizing the structure of mannotriose units in the backbone of GXM ; we suggest that this contact is required for killing of C. neoformans.

新生隐球菌是一种条件致病菌，属于担子菌类真菌，在细胞周期进程中具有独特的特性。在标准液体条件下，指数生长的C.新生儿期为132 ± 16分钟，G1、S、G2和M期的持续时间分别约为71、18、25和18分钟。DNA的合成始于芽萌发前，至芽长至母细胞1/4左右时完成。子细胞的倍增时间约为母细胞的两倍。G1 ~ G2期纺锤体位于核膜外，呈重复型。细胞周期蛋白依赖性激酶（Ddk）通过改变细胞的构象和生物学功能来调控细胞周期。Cdk也被认为可以结合或分离分子，特别是细胞周期蛋白，并改变酶的底物特异性。在新生隐球菌中，我们克隆了Cdk和cyclins蛋白，并通过计算机分析和构建了这两种蛋白之间的相互作用图谱。我们正在进一步分析C. neoformans Cdk和细胞周期蛋白C.金黄色葡萄球菌可杀死新生儿，可溶性荚膜多糖可抑制这种死亡。为了研究杀伤机制，在扫描和透射电子显微镜下检查共培养物中的细胞。S. aureus附着在C. neoformans的超微结构，以及附着的C. neoformans细胞具有死亡细胞的特征。我们鉴定了促进真菌-细菌相互作用的分子：S. aureus粘附在C.通过识别GXM骨架中甘露三糖单位的结构，我们认为这种接触是杀死C.新人类