Division of Parasitology, Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
Proteomics Clin Appl. 2008 Mar;2(3):372-86. doi: 10.1002/prca.200780017. Epub 2008 Feb 13.
Visceral leishmaniasis (VL) is the most devastating type caused by Leishmania donovani, Leishmania infantum, and Leishmania chagasi. The therapeutic mainstay is still based on the antiquated pentavalent antimonial against which resistance is now increasing. Unfortunately, due to the digenetic life cycle of parasite, there is significant antigenic diversity. There is an urgent need to develop novel drug/vaccine targets against VL for which the primary goal should be to identify and characterize the structural and functional proteins. Proteomics, being widely employed in the study of Leishmania seems to be a suitable strategy as the availability of annotated sequenced genome of Leishmania major has opened the door for dissection of both protein expression/regulation and function. Advances in clinical proteomic technologies have enable to enhance our mechanistic understanding of virulence/pathogenicity/host-pathogen interactions, drug resistance thereby defining novel therapeutic/vaccine targets. Expression proteomics exploits the differential expression of leishmanial proteins as biomarkers for application towards early diagnosis. Further using immunoproteomics efforts were also focused on evaluating responses to define parasite T-cell epitopes as vaccine/diagnostic targets. This review has highlighted some of the relevant developments in the rapidly emerging field of leishmanial proteomics and focus on its future applications in drug and vaccine discovery against VL.
内脏利什曼病(VL)是由利什曼原虫、婴儿利什曼原虫和恰加斯利什曼原虫引起的最具破坏性的类型。治疗的主要方法仍然是基于古老的五价锑,而这种药物现在已经越来越耐药。不幸的是,由于寄生虫的双核生命周期,存在着显著的抗原多样性。因此,迫切需要针对内脏利什曼病开发新的药物/疫苗靶点,其主要目标应该是识别和表征结构和功能蛋白。蛋白质组学在利什曼原虫的研究中得到了广泛的应用,似乎是一种合适的策略,因为利什曼原虫主要有注释的测序基因组的可用性为蛋白质表达/调控和功能的剖析打开了大门。临床蛋白质组学技术的进步使我们能够增强对毒力/致病性/宿主-病原体相互作用、耐药性的机制理解,从而确定新的治疗/疫苗靶点。表达蛋白质组学利用利什曼原虫蛋白的差异表达作为生物标志物,应用于早期诊断。进一步的免疫蛋白质组学研究也集中在评估反应,以确定寄生虫 T 细胞表位作为疫苗/诊断靶点。本文综述了利什曼原虫蛋白质组学这一快速发展领域的一些相关进展,并重点介绍了其在针对内脏利什曼病的药物和疫苗发现中的未来应用。