AMEBIASIS--HOST-PARASITE INTERACTIONS IN VIRULENCE

阿米巴病——毒力中宿主与寄生虫的相互作用

• 批准号: 3085449
• 负责人: LAUREN J HERBERT
• 金额: $ 7.08万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3085449
• 关键词: Entamoeba histolytica; amebiasis; communicable disease diagnosis; diagnosis design /evaluation; genetic strain; host organism interaction; human subject; microorganism immunology; nucleic acid probes; polymerase chain reaction; restriction fragment length polymorphism; virulence; western blottings

Of the estimated 500 million people worldwide infected with Entamoeba histolytica, only 10% develop disease. Whether virulence is a function of host or parasite factors has long been debated. Evidence has mounted over the last decade that there are distinct nonpathogenic and pathogenic strains (classified into 'zymodemes' based on isoenzyme electrophoretic patterns) of E. histolytica. However, there is also evidence of nonpathogenic zymodemes converting to pathogenic zymodemes. The long range goal of the research is to understand the molecular basis of pathogenesis of E. histolytica, and in particular, whether all or only some strains can cause disease. To address this, we will develop, validate, and apply strain specific probes and immunodiagnostic methods to an epidemiologic study of amebiasis in Mexico City. In preliminary studies, probes to two genes, M17, which encodes an immuonodominant surface antigen, and the 16S rRNA gene, were able to differentiate strains with pathogenic from those with nonpathogenic zymodemes. These probes will be tested against clinical isolates, and the results compared with zymodeme analysis and clinical symptoms, to determine their utility as diagnostic tools for the epidemiologic study. M17 fusion peptides have been synthesized and will be used to develop immunodiagnostic assays to measure total serum immunoglobulin and secretory IgA production. The assays will be used to monitor the gastrointestinal and serologic immune response to infection by different strains. In the epidemiologic study strain type will be correlated with symptoms and host immune response to determine whether only some strains are associated with disease, or whether a single strain can convert from nonpathogenic to pathogenic phenotype. The answers to these questions are important in developing treatment guidelines for asymptomatic carriers.

全球估计有5亿人中有5亿人中有 Entamoeba Histolictica，只有10％的疾病。 是否毒力 长期以来一直在争论宿主或寄生虫因素的函数。 在过去的十年中，有证据表明有独特的证据 非致病性和致病性菌株（分类为“ Zymodemes” 基于E. histolytica的同工酶电泳模式）。 但是，也有迹象表明非致病性Zymodemes 转化为致病性酶原体。 该研究的远距离目标是了解分子 组织溶血性大肠杆菌的发病机理，尤其是是否是否 所有或仅有的菌株都会引起疾病。 为了解决这个问题，我们 将开发，验证和应用特定的探针，并且 免疫诊断方法用于amebiasis流行病学研究 墨西哥城。 在初步研究中，对两个基因M17进行了探针，该基因编码一个 主体屈服的表面抗原和16S rRNA基因能够 使病原体与患有病原体区分开 非致病性Zymodemes。 这些探针将针对 临床分离株，结果与zymodeme分析相比 和临床症状，以确定其效用为诊断 流行病学研究的工具。 M17融合肽已合成，将用于 开发免疫诊断测定以测量总血清 免疫球蛋白和分泌IgA产生。 测定将是 用于监测胃肠道和血清学免疫反应 通过不同的菌株感染。 在流行病学研究中，应变类型将与 症状和宿主免疫反应以确定是否仅 菌株与疾病有关，或者单个菌株是否可以 从非致病性转变为致病表型。 答案 这些问题对于制定治疗指南很重要 无症状载体。