Treponema pallidum: Pathogenesis-associated molecules

梅毒螺旋体：发病机制相关分子

• 批准号: 7613422
• 负责人: Sheila A. Lukehart
• 金额: $ 36.52万
• 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 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7613422
• 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-Lymphocyte; 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，Treponema Pallidum，是梅毒，Yaws和Bejel的药物。 T. Carateum引起人类感染，Pinta。梅毒在发达国家引起流行病，并且在发展中国家是地方性的。估计每年有1200万人被感染。偏航，Bejel和Pinta发生在发展中国家的孤立地区，并且像梅毒一样，这些疾病会导致慢性残疾。 T. paraluiscuniculi与T. pallidum密切相关，并在兔子中引起性梅毒，但对人类不感染。在物种和亚种之间，这些致病性treponemes的感染和侵袭性的临床表现显着差异。此外，感染诱导的对致病性毛发的免疫力在物种或亚种之间是薄弱或不存在的，但在致病性毛素的亚种中更健壮。基于这些数据，我们认为独特的遗传序列定义了不同的临床疾病。同样，亚种之间相同的抗原不太可能完全保护性，而那些物种或亚种独有的抗原最有可能对完全保护至关重要。 TPR基因家族被认为与三链球炎感染的发病机理有关，并且我们已经鉴定了几个TPR基因中的亚种特异性序列。该更新应用提议1）使用聚焦基因测序识别TPR基因序列及其在三种t. pallidum的三种亚种的菌株以及相关的兔病原体T. paraluiscuniculi的菌株中的差异，并使用聚焦基因测序。 2）检验TPR基因的转录水平，在T. pallidum的三个亚种和T. paraluiscuniculi中，作为亚种/物种，组织位置以及感染后时间的函数。 3）确定选定的TPR抗原的T和B细胞表位，重点是菌株，亚种或致病性毛treponemes种之间序列不同的蛋白质。 4）确定在疫苗诱导的免疫中亚种或物种特异性TPR序列和基因表达的相对贡献。这些研究将导致对特定分子的鉴定，这些分子对领三蛋白酶感染和保护性免疫的发病机理很重要。 LAV语言的相关性：被称为Treponema的细菌每年在全球数百万人中引起几种不同，严重和持续的感染。这些研究将测试某些称为TPR基因的基因是否可用于从另一种感染中分辨一种感染，以及对这些细菌的免疫反应是否可以预防感染。