Sereno D, Cordeiro da Silva A, Mathieu-Daude F, Ouaissi A
IRD, UR008 Pathogénie des Trypanosomatidés, 911 Avenue Agropolis, BP 64501, 34394 Montpellier Cedex 5, France.
Parasitol Int. 2007 Mar;56(1):3-7. doi: 10.1016/j.parint.2006.09.001. Epub 2006 Oct 31.
Efforts for the development of new therapeutics, essential for the control of leishmaniasis rely mainly on screening of potentially effective compounds in pathogen growth/multiplication assays, both in vitro and in vivo. Screenings designed to closely reflect the situation in vivo are currently labor-intensive and expensive, since they require intracellular amastigotes and animal models. Screenings designed to facilitate rapid testing of a large number of drugs are not performed on the clinically relevant parasite stage, but the promastigotes. The ability to select transgenic Leishmania expressing reporter proteins, such as the green fluorescent protein (GFP) or the luciferase, opened up new possibilities for the development of drug screening tests. In this review we will focus on available methodologies for direct drug screening purposes against the mammalian stage of the parasite, with emphasis on the future developments that could improve sensitivity, reliability, versatility and the throughput of the intracellular model screening.
开发新疗法对于控制利什曼病至关重要,其主要依赖于在体外和体内病原体生长/增殖试验中筛选潜在有效的化合物。旨在密切反映体内情况的筛选目前劳动强度大且成本高,因为它们需要细胞内无鞭毛体和动物模型。旨在促进大量药物快速检测的筛选并非在临床相关的寄生虫阶段(即前鞭毛体)进行。选择表达报告蛋白(如绿色荧光蛋白(GFP)或荧光素酶)的转基因利什曼原虫的能力为药物筛选试验的开发开辟了新的可能性。在本综述中,我们将重点关注针对寄生虫哺乳动物阶段进行直接药物筛选的可用方法,重点是未来可能提高细胞内模型筛选的灵敏度、可靠性、通用性和通量的发展。