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.

在本项目中，我们研究了线粒体2-半胱氨酸过氧化物酶（TPx-2）在疟疾寄生虫的生理作用，通过破坏人类恶性疟原虫的基因。基因破坏的寄生虫（Pf TPx-2 KO）在人红细胞中正常发育，并以与亲本菌株（FCR-3）相似的速率繁殖。tBOOH和替代氧化酶抑制剂（水杨基异羟肟酸和没食子酸正丙酯）在与抑制FCR-3菌株生长的浓度相似的浓度下抑制Pf TPx-2 KO的体外生长。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伯氏疟原虫中的同源基因。我们使用疟疾研究和参考试剂资源（MR 4）提供的pMD 204构建了基因破坏质粒。我们还制备了抗重组PbTPx-2的兔血清，用于分析破坏物的表型。KO实验目前正在我们实验室进行。进一步研究阐明TPx-2的作用将为疟疾寄生虫的生物学提供新的见解，并促进中断其生命周期的策略的发展。

项目成果

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

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.

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.

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-1 is involved in gametocyte development in Plasmodium berghei

• DOI: 10.1016/j.molbiopara.2006.02.018
• 发表时间: 2006-07-01
• 期刊: MOLECULAR AND BIOCHEMICAL PARASITOLOGY
• 影响因子: 1.5
• 作者: Yano, Kazuhiko;Komaki-Yasuda, Kanako;Kawazu, Shin-ichiro
• 通讯作者: Kawazu, Shin-ichiro