Genetic dissection of drug resistance in trypanosomes.
Genetic dissection of drug resistance in trypanosomes.
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DOI：
10.1017/s003118201300022x
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发表时间：
2013-10
期刊：
影响因子：
2.4
通讯作者：
Horn D
中科院分区：
文献类型：
--
作者：
Alsford S;Kelly JM;Baker N;Horn D
锥虫引起两种被忽视的热带病，美洲的恰加斯病和撒哈拉以南非洲的非洲锥虫病。近年来，大量的分子工具已经开发出来，能够对锥虫生物学的许多方面进行遗传解剖，包括对一些当前临床和兽药的抗性机制。这导致了关键耐药决定因素的鉴定和表征，包括抗布氏锥虫药物的转运体，美拉胂醇，喷他脒和依氟鸟氨酸，以及抗克氏锥虫药物硝呋替莫-苯并硝唑的激活剂。最近，测序技术的进步，加上布鲁氏锥虫临床相关血流形式中RNA干扰文库的发展，导致已知与抗锥虫药物直接或间接相互作用的蛋白质数量呈指数增长。在这篇综述中，我们讨论了这些发现和技术发展，这些技术发展将进一步改变我们对药物-锥虫相互作用的理解。获得的新知识应该为开发新的干预措施提供信息，以防治由这些寄生虫引起的毁灭性疾病。
The trypanosomes cause two neglected tropical diseases, Chagas disease in the Americas and African trypanosomiasis in sub-Saharan Africa. Over recent years a raft of molecular tools have been developed enabling the genetic dissection of many aspects of trypanosome biology, including the mechanisms underlying resistance to some of the current clinical and veterinary drugs. This has led to the identification and characterization of key resistance determinants, including transporters for the anti-Trypanosoma brucei drugs, melarsoprol, pentamidine and eflornithine, and the activator of nifurtimox-benznidazole, the anti-Trypanosoma cruzi drugs. More recently, advances in sequencing technology, combined with the development of RNA interference libraries in the clinically relevant bloodstream form of T. brucei have led to an exponential increase in the number of proteins known to interact either directly or indirectly with the anti-trypanosomal drugs. In this review, we discuss these findings and the technological developments that are set to further revolutionise our understanding of drug-trypanosome interactions. The new knowledge gained should inform the development of novel interventions against the devastating diseases caused by these parasites.