INHIBITION OF TRYPANOSOME GLYCOLYSIS BY A SERUM PROTEIN

非洲锥虫会给人和他们的牲畜带来致命的疾病。 采采类传播的原生动物威胁着5000万人的福祉 人和牛被排除在1000万平方公里的潮湿地带 和撒哈拉以南非洲的半湿润地带。非洲水牛在非洲繁衍生息 采采集栖息地和耐受感染的所有非洲品系 锥虫。这些动物将寄生虫血症维持在非常低的水平或 无法检测到的水平，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和 利用这些知识制定新的可持续战略，以 控制人畜锥虫病。我们的研究表明 一种MR为15万的非洲水牛血清蛋白选择性地抑制 锥虫体体外糖酵解导致ATP指数下降 内容，逐渐丧失依赖于ATP的细胞功能和 最终这些生物体会死亡。 我们现在将对锥虫杀灭蛋白(Tcp)、克隆和 表达编码该蛋白质的互补脱氧核糖核酸(CDNA)， 确定锥虫上的TCP结合位点，并确定 结合位点特异性抗体抑制锥虫体糖酵解。这个 研究表明，无论是tcDNA还是tcp结合位点都是特异的。 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.