INHIBITION OF TRYPANOSOME GLYCOLYSIS BY A SERUM PROTEIN

血清蛋白对锥虫糖酵解的抑制

基本信息

批准号：
2442596
负责人：
SAMUEL J BLACK
金额：
$ 18.08万
依托单位：
UNIVERSITY OF MASSACHUSETTS AMHERST
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-07-01 至 1999-06-30
项目状态：
已结题

项目摘要

African trypanosomes cause fatal disease in people and their livestock. The tsetse-transmitted protozoa threaten the well-being of 50 million people and exclude cattle from 10 million square kilometers of the humid and subhumid zones of sub-Saharan Africa. African buffalo thrive in the tsetse habitat and are tolerant of infection with all strains of African trypanosomes. These animals maintain parasitemia at a very low or undetectable level and show no signs of disease. Our goal is to elucidate the molecular basis for this resistance characteristic and exploit this knowledge to develop new and sustainable strategies to control trypanosomiasis in humans and their livestock. Our studies show that an African buffalo serum protein of Mr 150,000 selectively inhibits trypanosome glycolysis in vitro resulting in exponential decline in ATP content, a progressive loss of ATP-dependent cellular functions and eventually death of the organisms. We will now characterize the trypanocidal protein (TCP), clone and express complementary deoxyribonucleic acid (cDNA) encoding the protein, identify the binding site for TCP on trypanosomes and ascertain whether binding site-specific antibodies inhibit trypanosome glycolysis. The studies will indicate whether TCP-cDNA or TCP-binding site-specific antibodies have potential to affect prophylactic control of African trypanosomes.

非洲锥虫会给人类及其牲畜带来致命的疾病。采采蝇传播的原生动物威胁着 5000 万人的福祉人类和牛群被排除在 1000 万平方公里的潮湿地区之外和撒哈拉以南非洲的半湿润地区。非洲水牛在这片土地上茁壮成长采采蝇栖息地，能够耐受所有非洲菌株的感染锥虫。这些动物将寄生虫血症维持在非常低或检测不到的水平并且没有显示出疾病迹象。我们的目标是阐明这种耐药特性的分子基础，并利用这些知识制定新的可持续战略控制人类及其牲畜的锥虫病。我们的研究表明 150,000先生的非洲水牛血清蛋白选择性抑制体外锥虫糖酵解导致 ATP 呈指数下降含量，ATP依赖性细胞功能的逐渐丧失和最终导致生物体死亡。我们现在将描述杀锥虫蛋白 (TCP)、克隆和表达编码蛋白质的互补脱氧核糖核酸（cDNA），识别 TCP 在锥虫上的结合位点并确定是否结合位点特异性抗体抑制锥虫糖酵解。这研究将表明 TCP-cDNA 或 TCP 结合位点特异性抗体有可能影响非洲的预防控制锥虫。