Development of control methods for tick and tick-borne diseases by functional analyses of midgut tick bioactive molecules

通过中肠蜱生物活性分子的功能分析开发蜱和蜱传疾病的控制方法

基本信息

批准号：
16380209
负责人：
TSUJI Natoshi
金额：
$ 10.06万
依托单位：
National Agricultural Research Organization
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2007
项目状态：
已结题

项目摘要

Ticks must feed only on blood to obtain nutrients. Ticks as vectors are the most important ecto-parasites of domestic animals and are the second-most important vector only to mosquitoes among arthropods that transmit infectious diseases in human. Pathogens, including viruses, bacteria and parasites, are taken up with the blood meal and exposed to a potentially hostile environment in the tick's midgut before invading the epithelium. Vector ticks possess a unique system that enables them to digest large amounts of host blood and to transmit the pathogens to the host, suggesting the existence of evolutionally acquired proteolytic mechanisms. Functional analyses of tick bioactive molecules (TBM) from the midgut of the babesial parasite vector tick Haemaphysalis longicornis were performed.1. Molecular basis of tick blood feeding and digestionSeveral TBMs implicated in blood feeding and digestion. (1) Tick serine proteases contributed to hemolysis, the initial step of hemoglobin digestion. ( … More 2) Several proteases expressed in the midgut contributed to host hemoglobin digestion, suggesting existence of an enzyme cascade of proteolysis of host blood components. (3) Inhibition of Glutamine: fructose-6-phosphate aminotransferase limits chitin biosynthesis thereby disrupting cuticle growth and peritrophic matrix formation during blood feeding.2. TMBs play crucial roles in inhibiting the transmission of Babesia parasitesSeveral TBMs (longicin, longipain and H1Galec) implicated in parasite transmission. (1) longicin which is one of tick defensins has babesiacidal effect. (2) longipain controlled the number of babesia parasites for invasion into the midgut. (3) HIGalec was a possible receptor of parasites in the midgut.3. Generation of gene-knockdown ticksWe established RNA interference to knockdown longipain mRNA by dsRNA injection in H. longicornis. This method may allow a direct and efficient way of producing and identifying the loss-of-function of targeted genes as a reverse genetic tool. Less

壁虱必须仅以血液为食才能获取营养。作为矢量的滴答是家畜的最重要的寄生虫，是对人类传播感染性疾病的节肢动物中蚊子的第二重要载体。病原体，包括病毒，细菌和寄生虫，在入侵上皮之前就被吸收了血液粉，并暴露于tick虫中肠中的潜在敌对环境。矢量壁虱具有独特的系统，使他们能够消化大量宿主血液并将病原体传递给宿主，这表明存在循环获得的蛋白水解机制。从巴布西亚寄生虫载体tick tick tick tick longicornis的中肠生物活性分子（TBM）的功能分析进行了。1。在血液喂养和消化中实现的滴答血液喂养和消化性的TBM的分子基础。（1）tick丝氨酸蛋白酶有助于溶血，这是血红蛋白消化的第一步。（更多2）在中肠中表达的几种蛋白酶有助于宿主血红蛋白消化，这表明存在宿主血成分的蛋白水解酶的酶。（3）抑制谷氨酰胺：6-磷酸氨基转移酶的果糖限制了几丁质的生物合成，从而破坏了血液喂养过程中的角质层生长和亲核基质形成。2。 TMB在抑制寄生虫传播中实施的Babesia Parasitesseveral TBM（Longicin，Longipain和H1GAlec）的传播中扮演着至关重要的作用。（1）longicin是tick蛋白之一，具有Babesiacidal效应。（2）Longipain控制着贝贝西亚寄生虫的数量，以入侵中肠。（3）Higalec是中肠寄生虫的可能受体。3。 Gene-Knockdown Tickswe的产生通过H. longicornis中的DsRNA注入来建立RNA干扰，以敲除Longipain mRNA。该方法可以直接有效地产生和识别目标基因作为反向遗传工具的功能丧失。较少的