Treponema pallidum: Pathogenesis-associated molecules

梅毒螺旋体：发病机制相关分子

• 批准号: 7799928
• 负责人: Sheila A. Lukehart
• 金额: $ 36.14万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7799928
• 关键词: Affect; Antibody Formation; Antigens; Area; B-Lymphocyte Epitopes; Bacteria; Chronic; Clinical; Data; Disease; Doctor of Philosophy; Enzyme-Linked Immunosorbent Assay; Epidemic; Epitopes; Funding; Gene Expression; Gene Family; Genes; Genetic; Genetic Transcription; Globus Pallidus; Goals; Growth; Human; Immune response; Immunity; Individual; Infection; Laboratories; Language; Lead; Location; Lymphocyte Activation; Methods; Molecular; Order Spirochaetales; Oryctolagus cuniculus; Pathogenesis; Pinta; Proteins; Recombinants; Relative (related person); Reverse Transcriptase Polymerase Chain Reaction; Role; Serological; Site; Syphilis; T cell response; Testing; Time; Tissues; Treponema; Treponema pallidum; Treponemal Infections; Yaws; base; disability; pathogen; protein expression; response; tissue tropism; vaccine-induced immunity

DESCRIPTION (provided by applicant): Subspecies of the pathogenic spirochete, Treponema pallidum, are the agents of syphilis, yaws, and bejel. T. carateum causes the human infection, pinta. Syphilis causes epidemics in the developed world and is endemic in the developing world; an estimated 12 million people are infected every year. Yaws, bejel, and pinta occur in isolated areas of the developing world and, like syphilis, these diseases can cause chronic disability. T. paraluiscuniculi is closely related to T. pallidum and causes venereal syphilis in rabbits, but is not infectious for humans. The clinical manifestations of infection and invasiveness of these pathogenic treponemes are significantly different among species and subspecies. Moreover, infection-induced immunity against the pathogenic treponemes is weak or non-existent across species or subspecies, but is more robust within a subspecies of pathogenic treponeme. Based on these data, we have reasoned that unique genetic sequences define the different clinical diseases. Similarly, antigens that are identical among the subspecies are unlikely to be completely protective, while those antigens that are unique to species or subspecies are most likely to be critical for complete protection. The tpr gene family is thought to be relevant to pathogenesis of treponemal infection, and we have already identified subspecies-specific sequences in several tpr genes. This renewal application proposes to 1) Identify differences in the sequences of tpr genes and their encoded proteins among strains of the three subspecies of T. pallidum and in the related rabbit pathogen T. paraluiscuniculi, using focused gene sequencing. 2) Examine the levels of transcription of the tpr genes in the three subspecies of T. pallidum and in T. paraluiscuniculi, as a function of subspecies/species, tissue location, and time after infection. 3) Identify the T and B cell epitopes of selected Tpr antigens, focusing on those proteins that differ in sequence among strains, subspecies, or species of pathogenic treponemes. 4) Determine the relative contribution of subspecies- or species-specific Tpr sequences and gene expression in vaccine-induced immunity. These studies will lead to the identification of specific molecules that are important to the pathogenesis of treponemal infections and protective immunity. Relevance in lav language: Bacteria known as Treponema cause several different, serious and persistent infections in millions of people globally each year. These studies will test whether certain genes, called tpr genes, can be used to tell one infection from another and whether the immune response to these bacteria can protect against infection.

描述（由申请人提供）：致病性螺旋体的亚种，梅毒螺旋体，是梅毒，雅司病和bejel的病原体。carateum会引起人类感染，pinta。梅毒在发达国家引起流行病，在发展中国家流行；估计每年有1 200万人受到感染。雅司病、bejel和pinta发生在发展中国家的偏远地区，与梅毒一样，这些疾病可导致慢性残疾。副带绦虫与苍白球绦虫密切相关，在家兔中引起性梅毒，但对人类没有传染性。这些致病性密螺旋体感染的临床表现和侵袭性在不同种和亚种之间存在显著差异。此外，对致病性密螺旋体的感染诱导免疫在物种或亚种之间是弱的或不存在的，但在致病性密螺旋体的亚种内更为强大。根据这些数据，我们推断出独特的基因序列定义了不同的临床疾病。同样，在亚种中相同的抗原不太可能具有完全的保护作用，而那些物种或亚种特有的抗原很可能对完全保护至关重要。tpr基因家族被认为与螺旋体感染的发病机制有关，我们已经在几个tpr基因中确定了亚种特异性序列。本申请的目的是：1)利用重点基因测序技术，鉴定白球绦虫3个亚种菌株和相关家兔副月牙绦虫tpr基因序列及其编码蛋白的差异。2)检测三种镰状绦虫亚种和副月牙绦虫tpr基因转录水平与亚种/种、组织位置和感染后时间的关系。3)鉴定选定的Tpr抗原的T和B细胞表位，重点鉴定病原性密螺旋体菌株、亚种或种之间序列不同的蛋白。4)确定亚种或种特异性Tpr序列和基因表达在疫苗诱导免疫中的相对贡献。这些研究将导致识别对螺旋体感染发病机制和保护性免疫很重要的特定分子。被称为密螺旋体的细菌每年在全球数百万人中引起几种不同的、严重的和持续的感染。这些研究将测试被称为tpr基因的某些基因是否可以用来区分一种感染和另一种感染，以及对这些细菌的免疫反应是否可以防止感染。