Flagellar antigens of Trichomonas vaginalis

阴道毛滴虫鞭毛抗原

• 批准号: 6666587
• 负责人: PHILIP F JEMILOHUN
• 金额: $ 12.94万
• 依托单位: UNIVERSITY OF ARKANSAS AT PINE BLUFF
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6666587
• 关键词: SDS polyacrylamide gel electrophoresis; Trichomonas vaginalis; adhesin; antiserum; cell component structure /function; flagellum antigen; human tissue; immunoprecipitation; laboratory rabbit; parasite infection mechanism; protozoal antigen

DESCRIPTION (provided by the applicant): Of all the sexually transmitted diseases, Trichomoniasis is the most common non-viral infection. An estimated 200 million people are infected annually all over the world, with greater than four million new cases per year in the United States alone. The agent of the disease, Trichomonas vaginalis, is a protozoan parasite with four anterior flagella and a recurrent flagellum. Trichomoniasis has recently been associated with severe complications such as development of cervical cancer, high probability of infection by human immunodeficiency virus and adverse pregnancy outcomes. In spite of the high incidence of trichomoniasis and the complications associated with the disease, the mechanisms of pathogenesis of the parasite are not well understood and some drug resistant strains of T. vaginalis are emerging. Therefore, there is urgent need for research in the area of subcellular structures of the parasite for; (a) adhesion molecules whose antisera will be of prophylactic value (b) discovery of new targets for anti-parasitic drugs (c) better understanding (immunobiology and functions) of the subcellular structures of the parasite. Our Preliminary Studies revealed several flagellar polypeptides that showed strong immuno-reactivity with human anti-Trichomoniasis sera in immunoblots. Furthermore, studies from different laboratories have shown that T. vaginalis cells are immunogenic in humans and laboratory animals. Based on these reports and our Preliminary Studies we hypothesize that flagellar proteins of the parasite are involved in adhesion of the parasite to the host cells. This hypothesis will be tested by isolating flagella followed by immunoprecipitation and analysis of flagellar antigens on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SOSPAGE). The flagellar antigens will be used to immunize rabbits and the rabbit antisera will be utilized to screen the parasite for adhesion inhibition. Flagellar antigens whose antisera show significant degree of adhesion inhibition will be considered to be flagellar adhesins. The role of the adhesins as ligands in the cytoadhesion of the parasite to host cells will be tufty examined by adhesion/adhesion inhibition assays. The adhesins will be characterized to know if they are surface exposed and the biochemical make up of the reacting epitopes. It is anticipated that the results of these studies will yield new information about the roles of flagellar proteins in the pathogenesis of T. vaginatis.

描述（由申请人提供）：在所有性传播疾病中，三核菌病是最常见的非病毒感染。估计每年在全球每年被感染了2亿人，仅在美国，每年有超过400万例新病例。该疾病的药物是阴道滴虫，是一种原生动物寄生虫，有四个前鞭毛和一个复发性的鞭毛。龙核病病最近与严重的并发症有关，例如宫颈癌的发展，人类免疫缺陷病毒感染的可能性很高以及不良妊娠结局。尽管滴虫病的发生率很高，并且与疾病相关的并发症，但寄生虫发病机理的机制尚未得到充分了解，并且某些阴道的抗药性菌株正在出现。因此，迫切需要在寄生虫的亚细胞结构领域进行研究； （a）抗血清的粘附分子将具有预防价值（b）发现抗寄生虫亚细胞结构的抗寄生液药物的新靶标（C）更好地理解（免疫生物学和功能）。我们的初步研究揭示了几种鞭毛多肽，这些多肽在免疫印迹中与人类抗三核病患者血清具有强烈的免疫反应性。此外，来自不同实验室的研究表明，阴道细胞在人类和实验动物中具有免疫原性。基于这些报告和初步研究，我们假设寄生虫的鞭毛蛋白参与寄生虫对宿主细胞的粘附。该假设将通过分离鞭毛，然后对十二烷基硫酸钠聚丙烯酰胺凝胶电泳（Sopsage）进行免疫沉淀和分析。鞭毛抗原将用于免疫兔子，兔抗原将用于筛选寄生虫以进行粘附抑制。抗抗血清表现出很大程度的粘附抑制作用的鞭毛抗原将被视为鞭毛粘附素。粘附素作为配体在寄生虫对宿主细胞的细胞粘附中的作用将通过粘附/粘附抑制测定法检查。粘附素将被表征为知道它们是否表面暴露，并且反应表位的生化构成。预计这些研究的结果将产生有关鞭毛蛋白在T. caginatis发病机理中的作用的新信息。