Kumari Shraddha, Kumar Awanish, Samant Mukesh, Singh Neeloo, Dube Anuradha
Division of Parasitology, Central Drug Research Institute, Post Box No. 173, Lucknow-226001, India.
Curr Drug Targets. 2008 Nov;9(11):938-47. doi: 10.2174/138945008786786091.
Among the three clinical forms (cutaneous, mucosal and visceral) of leishmaniasis visceral (VL) one is the most devastating type caused by the invasion of the reticuloendothelial system of human by Leishmania donovani, L. infantum and L. chagasi. India and Sudan account for about half the world's burden of VL. Current control strategy is based on chemotherapy, which is difficult to administer, expensive and becoming ineffective due to the emergence of drug resistance. An understanding of resistance mechanism(s) operating in clinical isolates might provide additional leads for the development of new drugs. Further, due to the lack of fully effective treatment the search for novel immune targets is also needed. So far, no vaccine exists for VL despite indications of naturally developing immunity. Therefore, an urgent need for new and effective leishmanicidal agents and for this identification of novel drug and vaccine targets is imperative. The availability of the complete genome sequence of Leishmania has revolutionised many areas of leishmanial research and facilitated functional genomic studies as well as provided a wide range of novel targets for drug designing. Most notably, proteomics and transcriptomics have become important tools in gaining increased understanding of the biology of Leishmania to be explored on a global scale, thus accelerating the pace of discovery of vaccine/drug targets. In addition, these approaches provide the information regarding genes and proteins that are expressed and under which conditions. This review provides a comprehensive view about those proteins/genes identified using proteomics and transcriptomic tools for the development of vaccine/drug against VL.
在利什曼病的三种临床形式(皮肤型、黏膜型和内脏型)中,内脏利什曼病(VL)是最具破坏性的一种,它由杜氏利什曼原虫、婴儿利什曼原虫和恰加斯利什曼原虫入侵人体的网状内皮系统引起。印度和苏丹的VL负担约占全球的一半。目前的控制策略基于化疗,化疗难以实施、费用高昂,而且由于耐药性的出现正变得无效。了解临床分离株中起作用的耐药机制可能为新药开发提供更多线索。此外,由于缺乏完全有效的治疗方法,寻找新的免疫靶点也很有必要。到目前为止,尽管有自然产生免疫力的迹象,但尚无针对VL的疫苗。因此,迫切需要新的有效的杀利什曼原虫剂,为此确定新的药物和疫苗靶点势在必行。利什曼原虫完整基因组序列的可得性彻底改变了利什曼原虫研究的许多领域,促进了功能基因组学研究,并为药物设计提供了广泛的新靶点。最值得注意的是,蛋白质组学和转录组学已成为在全球范围内增进对利什曼原虫生物学理解的重要工具,从而加快了疫苗/药物靶点的发现步伐。此外,这些方法提供了有关表达的基因和蛋白质以及表达条件的信息。本综述全面介绍了利用蛋白质组学和转录组学工具鉴定的那些用于开发抗VL疫苗/药物的蛋白质/基因。