Analysis of the effects of the disruption of the mitochondrial antioxidant protein gene on development of malaria parasite

线粒体抗氧化蛋白基因破坏对疟原虫发育的影响分析

• 批准号: 18590412
• 负责人: KAWAZU Shin-Ichiro
• 金额: $ 2.57万
• 依托单位: Obihiro University of Agriculture and Veterinary Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590412/
• 关键词: Infectious diseases; Malaria; Mitochondria; Redox; Transgenic parasite

In this project, we investigated the physiologic role of mitochondrial 2-Cys peroxiredoxin (TPx-2) in malaria parasite by disrupting the gene in the human malaria parasite Plasmodium falciparum. The gene-disrupted parasite (Pf TPx-2 KO) developed normally in human erythrocytes and multiplied at a rate similar to that of the parent strain (FCR-3). The in vitro growth of Pf TPx-2 KO was inhibited by tBOOH and alternative oxidases inhibitors (Salicylhydroxamic acid and n-propyl gallate) at concentrations similar to those inhibit the growth of FCR-3 strain. To investigate the importance of TPx-2 in the parasite life cycle in vivo, we tried to disrupt the homologous-gene in the rodent malaria parasite Plasmodium berghei. We constructed the gene disruption plasmid using pMD204, which was provided by Malaria Research and Reference Reagent Resource (MR4). We also prepared anti-recombinant PbTPx-2 rabbit serum for analyzing phenotype of the disruptant. The KO experiment is currently under way in our laboratory. Further studies clarifying the roles of TPx-2 will provide new insight into the biology of malaria parasites and facilitate development of strategies to interrupt their life cycle.

在该项目中，我们通过破坏人类疟原虫疟原虫恶性疟原虫中的基因来研究线粒体2-Cys氧蛋白（TPX-2）在疟疾寄生虫中的生理作用。基因 - 脱离的寄生虫（PF TPX-2 KO）正常在人类红细胞中开发，并以类似于父菌株（FCR-3）的速率乘以。 TBOOH抑制PF TPX-2 KO的体外生长，替代性氧化酶抑制剂（水杨羟基酸和N-丙酰胺）的浓度与抑制FCR-3菌株的生长相似。为了研究TPX-2在体内寄生虫生命周期中的重要性，我们试图破坏啮齿动物疟原虫寄生虫疟原虫berghei中的同源基因。我们使用PMD204构建了基因破坏质粒，该质粒由疟疾研究和参考试剂资源（MR4）提供。我们还制备了抗脱组成的PBTPX-2兔子血清，以分析破坏性的表型。我们的实验室目前正在进行KO实验。进一步的研究阐明了TPX-2的作用，将为疟疾寄生虫的生物学提供新的见解，并促进开发中断其生命周期的策略。

项目成果

Identification of proteins targeted by cytoplasmic thioredoxin in Plasmodium falciparum.

恶性疟原虫细胞质硫氧还蛋白靶向蛋白质的鉴定。

• 发表时间: 2006
• 作者: Kawazu;S.;et. al.
• 通讯作者: et. al.

マラリア原虫細胞質でチオレドキシンと相互作用するタンパク質の同定

鉴定与疟疾寄生虫细胞质中硫氧还蛋白相互作用的蛋白质

• 发表时间: 2006
• 作者: 河津信一郎;他
• 通讯作者: 他

Evaluation of blood preservation methods in the. performance of the who in vitro micro-test for Plasmodium falciparum in the field

血液保存方法的评价。

• 发表时间: 2008
• 期刊: Tropical Medicine and Health (In press)
• 作者: Iwagami;M.;et. al.
• 通讯作者: et. al.

2-Cys peroxiredoxin TPx-l is involved in gametocyte development in Plasmodium berghei.

2-Cys 过氧化还原蛋白 TPx-1 参与伯氏疟原虫配子体的发育。

• 发表时间: 2006
• 作者: Kawazu;S. ;et. al.
• 通讯作者: et. al.

2-Cys型ペルオキシレドキシン(TPx-1)ノックアウトがマラリア原虫のオーシスト発育に及ぼす影響の解析

2-Cys过氧化还原蛋白（TPx-1）敲除对疟原虫卵囊发育的影响分析

• 发表时间: 2006
• 作者: 矢野和彦;他
• 通讯作者: 他