Swiss Tropical and Public Health Institute, Basel, Switzerland.
University of Basel, Switzerland.
FEBS J. 2018 Mar;285(6):1012-1023. doi: 10.1111/febs.14302. Epub 2017 Nov 13.
Trypanosoma brucei comprise the causative agents of sleeping sickness, T. b. gambiense and T. b. rhodesiense, as well as the livestock-pathogenic T. b. brucei. The parasites are transmitted by the tsetse fly and occur exclusively in sub-Saharan Africa. T. brucei are not only lethal pathogens but have also become model organisms for molecular parasitology. We focus here on membrane transport proteins of T. brucei, their contribution to homeostasis and metabolism in the context of a parasitic lifestyle, and their pharmacological role as potential drug targets or routes of drug entry. Transporters and channels in the plasma membrane are attractive drug targets as they are accessible from the outside. Alternatively, they can be exploited to selectively deliver harmful substances into the trypanosome's interior. Both approaches require the targeted transporter to be essential: in the first case to kill the trypanosome, in the second case to prevent drug resistance due to loss of the transporter. By combining functional and phylogenetic analyses, we were mining the T. brucei predicted proteome for transporters of pharmacological significance. Here, we review recent progress in the identification of transporters of lipid precursors, amino acid permeases and ion channels in T. brucei.
布氏锥虫包括昏睡病的病原体，即冈比亚锥虫和罗得西亚锥虫，以及家畜病原体布氏锥虫。寄生虫通过采采蝇传播，仅存在于撒哈拉以南非洲。布氏锥虫不仅是致命的病原体，而且还成为了分子寄生虫学的模式生物。我们在这里重点关注布氏锥虫的膜转运蛋白，它们在寄生生活方式下对维持体内平衡和代谢的贡献，以及它们作为潜在药物靶点或药物进入途径的药理学作用。质膜中的转运蛋白和通道是有吸引力的药物靶点，因为它们可以从外部进入。或者，它们可以被利用来选择性地将有害物质输送到原生动物的内部。这两种方法都需要靶向转运蛋白是必需的：在第一种情况下杀死原生动物，在第二种情况下防止由于转运蛋白丢失而产生耐药性。通过结合功能和系统发育分析，我们从 T. brucei 预测的蛋白质组中挖掘出具有药理学意义的转运蛋白。在这里，我们综述了最近在鉴定 T. brucei 中脂质前体、氨基酸渗透酶和离子通道的转运蛋白方面的进展。
