巴贝斯虫病是由多种巴贝斯虫引起的一类危害人畜健康的血液原虫病，目前控制该病无有效药物，故寻找和开发新药靶和新药物是该病研究的重点。已知原虫通过不同于宿主甲羟戊酸（MVA）途径的非甲羟戊酸（MEP）途径合成异戊二烯焦磷酸（IPP）供生命所需，故阻断其IPP合成抑制虫体生长成为开发新药的潜在途径。前期研究发现东方巴贝斯虫存在MEP途径，但对其限速酶的功能一无所知。本研究拟克隆该途径关键限速酶1-脱氧-D-木酮糖-5-磷酸还原异构酶(DXR)，通过酶活、抑制剂实验等探索该酶功能；通过蛋白定位检测其在东方巴贝斯虫不同时期的表达特征；以大肠杆菌为模型，构建BoDXR遗传互补株，通过菌落群数、生长曲线检测其功能位点，利用现有药物库筛选抑制剂评价抑制效率；用筛选的抑制剂进行东方巴贝斯虫生长抑制实验，通过染虫率虫体存活时间等鉴定DXR对虫体存活的重要性，从而为巴贝斯虫药物设计提供理论依据和新的模型及思路。

Babesiosis is a tick-transmitted disease caused by protozoans of the genus Babesia. It’s a heamoparasite disease with a world-wide distribution infecting many species of mammals and humans. Babesiosis is mainly controlled by drugs nowadays. However, all current drugs have toxicity and side effects. Search and development of new drugs is the key point of controlling this disease. All cells require the Isopentenyl diphosphate (IPP) synthesized by themselves to support their life activities. It’s reported that protozoan parasites synthesize IPP by methylerythritol phosphate (MEP) pathway, which is totally different from the mevalonate (MVA) pathway used by their hosts. Thus inhibiting the MEP pathway is a potential new strategy for anti-parasitic drug discovery. Our previous work on genome analysis of Babesia orientalis suggested the presence of the MEP pathway in this parasite. In this study, we plan to investigate the biological significance of DXR in Babesia orientalis. We will clone and recombinantly express the rate-limiting enzymes DXR from B. orientalis, test their enzyme activities and screen chemical inhibitors in vitro and examine their cellular localization in vivo. Since bacteria such as E. coli also use the MEP pathway for IPP production, we plan to use E. coli as a model to characterize these two enzymes. Replace DXR in E. coli with corresponding enzymes from B. orientalis and test the growth of E. coli under different conditions (such as with or without inhibitors) to assess their enzymatic properties in vivo. Subsequently use chemical inhibitors for DXR and test their impact on parasite growth to address the biological importance of the MEP pathway for parasite survival. Completion of this work will provide significant insights into anti-babesiosis drug design.