How do malarial parasites invade target organs of the vector mosquito?
疟疾寄生虫如何侵入媒介蚊子的目标器官?
基本信息
- 批准号:16390124
- 负责人:
- 金额:$ 9.54万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:2004
- 资助国家:日本
- 起止时间:2004 至 2005
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
After ingestion of infected blood by a mosquito, malarial parasites are fertilized in the mosquito midgut and develop into motile ookinetes. These ookinetes invade epithelial cells by rupturing the cell membrane and migrate through the cytoplasm toward the basal lamina, on which they develop to oocysts. In this study we found that a microneme protein with a membrane-attack complex and perforin (MACPF) -related domain, which we name membrane-attack ookinete protein (MAOP), is produced in the ookinete stage and plays an essential role in midgut invasion by the ookinete. Ookinetes with the MAOP gene disrupted completely lost infectivity to the midgut. After ingestion of blood infected with the disrupted parasite, the midgut epithelium remained intact, making a clear contrast with the damaged midgut epithelium invaded by wild-type ookinetes. Electron microscopic analysis showed that the disruptant ookinetes migrate to the gut epithelium and attach to the cell surface at the apical tip, but are unable to enter the cytoplasm by rupturing the cell membrane. These results indicate that the MAOP molecule acts on the plasma membrane of the host-cell-like mammalian MACPF family proteins that create pores in the membrane of target cells. Another previously identified MACPF-related molecule (SPECT2) is produced in the liver-infective sporozoite and has a crucial role in traversing the liver sinusoidal cell boundary. The present finding, thus, suggests that conserved mechanisms for membrane rupture involving MACPF-related proteins are used in different host invasive stages of the malarial parasite, playing a key role in breaching biological barriers of host organs.
在蚊子摄入受感染的血液后,疟疾寄生虫在蚊子中肠中受精并发育成能动的动卵细胞。这些动合子通过破坏细胞膜侵入上皮细胞,并通过细胞质向基膜迁移,在基膜上发育成卵囊。在这项研究中,我们发现,微线蛋白与膜攻击复合物和穿孔素(MACPF)相关的结构域,我们命名为膜攻击动合子蛋白(MAOP),是在动合子阶段产生的,并在中肠入侵的动合子起着至关重要的作用。MAOP基因被破坏的动合子完全失去了对中肠的感染力。在摄入被破坏的寄生虫感染的血液后,中肠上皮保持完整,与野生型动合子侵入的受损中肠上皮形成鲜明对比。电子显微镜分析表明,破坏性动合子迁移到肠上皮细胞,并附着在顶端的细胞表面,但不能通过破坏细胞膜进入细胞质。这些结果表明,MAOP分子作用于宿主细胞样哺乳动物MACPF家族蛋白的质膜上,所述MACPF家族蛋白在靶细胞的膜中产生孔。另一个先前鉴定的MACPF相关分子(SPECT2)在肝脏感染的子孢子中产生,并在穿越肝窦细胞边界中起关键作用。因此,本研究结果表明,膜破裂涉及MACPF相关蛋白的保守机制用于疟原虫的不同宿主侵入阶段,在突破宿主器官的生物屏障中发挥关键作用。
项目成果
期刊论文数量(18)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A Plasmodium sporozoite protein with a membrane for malarial parasites to commit to infection of the hepatocyte.
一种疟原虫子孢子蛋白,具有膜,使疟疾寄生虫能够感染肝细胞。
- DOI:
- 发表时间:2005
- 期刊:
- 影响因子:0
- 作者:Ishino T;Chinzei Y;Yuda M
- 通讯作者:Yuda M
Liver invasion by malarial parasites--how do malarial parasites break through the host barrier
疟原虫入侵肝脏——疟原虫如何突破宿主屏障
- DOI:
- 发表时间:2004
- 期刊:
- 影响因子:0
- 作者:Yuda M;Ishino T
- 通讯作者:Ishino T
Essential role of membrane- attack protein in malarial trnsmission to mosquito host.
膜攻击蛋白在疟疾向蚊子宿主传播中的重要作用。
- DOI:
- 发表时间:2005
- 期刊:
- 影响因子:0
- 作者:Kadota K;Ishino T;Matsuyama T;Chinzei Y;Yuda M
- 通讯作者:Yuda M
Two proteins with 6-cys motifs are required for malarial parasites to commit to infection of the hepatocyte
- DOI:10.1111/j.1365-2958.2005.04801.x
- 发表时间:2005-12-01
- 期刊:
- 影响因子:3.6
- 作者:Ishino, T;Chinzei, Y;Yuda, M
- 通讯作者:Yuda, M
CelTOS, a novel malarial protein that mediates transmission to mosquito and vertebrate hosts
- DOI:10.1111/j.1365-2958.2005.05024.x
- 发表时间:2006-03-01
- 期刊:
- 影响因子:3.6
- 作者:Kariu, T;Ishino, T;Yuda, M
- 通讯作者:Yuda, M
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{{ truncateString('YUDA Masao', 18)}}的其他基金
Development of a direct transfection method in Plasmodium falciparum
恶性疟原虫直接转染方法的开发
- 批准号:
23659210 - 财政年份:2011
- 资助金额:
$ 9.54万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Exploration of malaria parasite genes involved in host-invasion using a transcription factor as a clue
以转录因子为线索探索参与宿主入侵的疟原虫基因
- 批准号:
20249023 - 财政年份:2008
- 资助金额:
$ 9.54万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Investigation of liver infection mechanisms of malaria parasites
疟疾寄生虫肝脏感染机制的研究
- 批准号:
18390128 - 财政年份:2006
- 资助金额:
$ 9.54万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Investigation of the molecular mechanisms of malarial ookinete invasion into the mosquite midgut epithelium in the rodent mararial parasite, Plasmodium berghei
疟原虫动动分子侵入啮齿类疟原虫伯氏疟原虫中肠上皮细胞的分子机制研究
- 批准号:
12470060 - 财政年份:2000
- 资助金额:
$ 9.54万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Analyses of characterization and structure of NO synthase and NO-carrier protein from blood-sucking insects
吸血昆虫NO合成酶和NO载体蛋白的特性和结构分析
- 批准号:
10670227 - 财政年份:1998
- 资助金额:
$ 9.54万 - 项目类别:
Grant-in-Aid for Scientific Research (C)