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后基因组时代恶性疟原虫耐药性的功能分析

Functional analysis of drug resistance in Plasmodium falciparum in the post-genomic era.

作者信息

Cowman A F

机构信息

The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Royal Parade, Melbourne, Victoria 3050, Australia.

出版信息

Int J Parasitol. 2001 Jul;31(9):871-8. doi: 10.1016/s0020-7519(01)00201-6.

DOI:10.1016/s0020-7519(01)00201-6
PMID:11406136
Abstract

Malaria has plagued humans throughout recorded history and results in the death of over 2 million people per year. The protozoan parasite Plasmodium falciparum causes the most severe form of malaria in humans. Chemotherapy has become one of the major control strategies for this parasite; however, the development of drug resistance to virtually all of the currently available drugs is causing a crisis in the use and deployment of these compounds for prophylaxis and treatment of this disease. The genome sequence of P. falciparum is providing the informational base for the use of whole-genome strategies such as bioinformatics, microarrays and genetic mapping. These approaches, together with the availability of a high-resolution genome linkage map consisting of hundreds of microsatellite markers and the advanced technologies of transfection and proteomics, will facilitate an integrated approach to address important biological questions. In this review we will discuss strategies to identify novel genes involved in the molecular mechanisms used by the parasite to circumvent the lethal effect of current chemotherapeutic agents.

摘要

自有记载的历史以来,疟疾就一直困扰着人类,每年导致超过200万人死亡。原生动物寄生虫恶性疟原虫会引发人类最严重的疟疾形式。化疗已成为针对这种寄生虫的主要控制策略之一;然而,几乎对所有现有药物产生耐药性的情况正在引发一场危机,即这些化合物在预防和治疗该疾病时的使用和部署问题。恶性疟原虫的基因组序列为诸如生物信息学、微阵列和基因图谱绘制等全基因组策略的应用提供了信息基础。这些方法,再加上由数百个微卫星标记组成的高分辨率基因组连锁图谱的可用性以及转染和蛋白质组学等先进技术,将有助于采用综合方法来解决重要的生物学问题。在本综述中,我们将讨论识别参与寄生虫用于规避当前化疗药物致死效应的分子机制的新基因的策略。

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