INHIBITION OF TRYPANOSOME GLYCOLYSIS BY A SERUM PROTEIN

非洲锥虫在人和牲畜中引起致命疾病。 采采蝇传播的原生动物威胁着5000万人的健康 人们和牛被排除在1000万平方公里的潮湿 以及撒哈拉以南非洲的半湿润地区。 非洲布法罗在 采采蝇栖息地和耐受感染的所有菌株的非洲 锥虫 这些动物将寄生虫血症维持在非常低或 无法检测到的水平，并显示没有疾病的迹象。 我们的目标是 阐明这种抗性特征的分子基础， 利用这些知识制定新的可持续战略， 控制人类和家畜的锥虫病。 我们的研究表明 一只Mr为150，000的非洲布法罗血清蛋白 体外锥虫糖酵解导致ATP指数下降 内容，ATP依赖性细胞功能的进行性丧失， 最终导致生物体死亡。 我们现在将表征杀锥虫蛋白（TCP），克隆和 表达编码该蛋白的互补脱氧核糖核酸（cDNA）， 确定锥虫上TCP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。 的 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性控制， 锥虫

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.