Identification of E. histolytica virulence factors

描述（由申请人提供）：每十个人中就有一个死于腹泻病 在孟加拉国等贫穷国家，五岁以上的儿童。 溶组织内阿米巴是病原体之一。它是人类的寄生虫 它具有入侵和溶解宿主组织的非凡能力侵入性 感染E.溶组织菌导致痢疾、阿米巴结肠炎和阿米巴 肝脓肿内阿米巴基因组计划即将完成 提供了一个前所未有的机会，应用遗传学的方法， 阿米巴病的问题。提出了三个具体目标：（1）表征 宿主：寄生虫界面通过识别分子招募到这个网站， 急诊（2）使用酵母双杂交系统， 蛋白质组学方法结合E.溶组织菌基因组测序 数据库，以进一步表征与GalNAc相互作用的新型蛋白质 （3）探讨E. histolytica 由GalNAc凝集素募集到宿主：寄生虫界面的蛋白质， 使用干扰RNA（RNAi）产生这些蛋白质的“敲除”突变体， 反义RNA技术和/或显性失活突变体的表达。 成功完成这些研究将产生一个基本的理解 与E.溶组织GalNAc凝集素和 它们在致病性中的作用。

DESCRIPTION (provided by applicant): Diarrheal diseases kill one of every ten children by his or her fifth birthday in poor countries such as Bangladesh. Entamoeba histolytica is one of the etiologic agents. It is a human parasite that has a remarkable ability to invade and lyse host tissues. Invasive infection with E. histolytica leads to dysentery, amebic colitis, and amebic liver abscess. The imminent completion of the Entamoeba genome project provides an unprecendented opportunity to apply the approaches of genetics to the problem of amebiasis. Three specific aims are proposed: (1) Characterize the host:parasite interface by identifying molecules recruited to this site by the E. histolytica GalNAc lectin using a yeast two-hybrid system, (2) Use a proteomics approach in conjunction with the E. histolytica genome sequencing database to further characterize novel proteins that interact with the GalNAc lectin, and (3) Investigate the biological significance of E. histolytica proteins recruited by the GalNAc lectin to the host:parasite interface by creating "knockout" mutants of these proteins using interference RNA (RNAi), antisense RNA technology, and/or expression of dominant negative mutants. Successful completion of these studies will yield a fundamental understanding of amebic proteins that interact with the E. histolytica GalNAc lectin and their role in pathogenicity.