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利什曼原虫及其宿主哺乳动物细胞的同步多参数分析:一种基于高内涵成像的方法,助力可靠的药物发现过程。

Simultaneous multi-parametric analysis of Leishmania and of its hosting mammal cells: A high content imaging-based method enabling sound drug discovery process.

作者信息

Forestier Claire-Lise, Späth Gerald Frank, Prina Eric, Dasari Sreekanth

机构信息

INSERM U1095, URMITE-UMR CNRS 7278, Infectiopole Sud, University of Aix-Marseille, Marseille, France.

Institut Pasteur and CNRS URA2581, Unité de Parasitologie moléculaire et Signalisation, Paris, France.

出版信息

Microb Pathog. 2015 Nov;88:103-8. doi: 10.1016/j.micpath.2014.10.012. Epub 2014 Oct 31.

Abstract

Leishmaniasis is a vector-borne disease for which only limited therapeutic options are available. The disease is ranked among the six most important tropical infectious diseases and represents the second-largest parasitic killer in the world. The development of new therapies has been hampered by the lack of technologies and methodologies that can be integrated into the complex physiological environment of a cell or organism and adapted to suitable in vitro and in vivo Leishmania models. Recent advances in microscopy imaging offer the possibility to assess the efficacy of potential drug candidates against Leishmania within host cells. This technology allows the simultaneous visualization of relevant phenotypes in parasite and host cells and the quantification of a variety of cellular events. In this review, we present the powerful cellular imaging methodologies that have been developed for drug screening in a biologically relevant context, addressing both high-content and high-throughput needs. Furthermore, we discuss the potential of intra-vital microscopy imaging in the context of the anti-leishmanial drug discovery process.

摘要

利什曼病是一种媒介传播疾病,目前可用的治疗选择有限。该疾病位列六大最重要的热带传染病之中,是世界上第二大致命寄生虫病。由于缺乏能够融入细胞或生物体复杂生理环境并适用于合适的体外和体内利什曼原虫模型的技术和方法,新疗法的开发受到了阻碍。显微镜成像技术的最新进展为评估潜在候选药物对宿主细胞内利什曼原虫的疗效提供了可能。这项技术能够同时可视化寄生虫和宿主细胞中的相关表型,并对各种细胞事件进行定量分析。在本综述中,我们介绍了为在生物学相关背景下进行药物筛选而开发的强大细胞成像方法,以满足高内涵和高通量的需求。此外,我们还讨论了在抗利什曼原虫药物发现过程中活体显微镜成像的潜力。

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