Pathogenesis of Persistent Chlamydial STDs

持续性衣原体性传播疾病的发病机制

基本信息

批准号：
7151468
负责人：
DEBORAH Anne DEAN
金额：
$ 23.6万
依托单位：
CHILDREN'S HOSPITAL & RES CTR AT OAKLAND
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-15 至 2008-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7151468
关键词：
Adolescent Adopted Amino Acid Sequence Homology Anabolism Antigenic Variation Baltimore Biology California Cervical Chaperonin 60 Chlamydia Chlamydia trachomatis Chlamydiaceae Chlamydophila pneumoniae Chlamydophila psittaci Cities Clinical DNA DNA Databases DNA Microarray Chip DNA Microarray format Data Development Dioxygenases Disease Dot Immunoblotting Ectopic Pregnancy Enzymes Epidemiologic Studies Epidemiology Evolution Face Family Gene Proteins Genes Genetic Genetic Databases Genetic Polymorphism Genome Genotype Grant Human Resources In Vitro Infection Infertility Inflammation Institutes Instruction Interferon Type II Interferons Intervention Investigation Knowledge Last Name Lead Link Lipopolysaccharides Location Maryland Membrane Proteins Messenger RNA Molecular Profiling Mouse Strains Names Nucleotides Numbers Open Reading Frames Operon Organism Outcome Pathogenesis Pathology Patients Pattern Pediatric Hospitals Pelvic Inflammatory Disease Phenotype Play Postdoctoral Fellow Principal Investigator Printing Proteins Publishing Reading Recombinant Proteins Recurrence Research Research Institute Research Personnel Research Project Grants Research Proposals Reverse Transcriptase Polymerase Chain Reaction Risk Role Sampling Screening procedure Serological Serotyping Serum Sexually Transmitted Diseases Site Students Taxonomy Time Tryptophan Tryptophan Synthase United States Universities Variant Virginia Virulence Woman base cost genetic evolution genetic profiling genome sequencing immunogenic in vivo indoleamine insertion/deletion mutation interest major outer membrane protein member microbial polyclonal antibody programs protein expression prototype rRNA Genes tool young adult

项目摘要

Chlamydia trachomatis(CT) is the leading cause of sexually transmitted diseases (STD) in the developed world. CT infections and their sequelae of pelvic inflammatory disease, ectopic pregnancy, and infertility are responsible for ~80% of the estimated $2.5 billion annual cost of these infections in the United States. Further, up to 50% of women become reinfected and are at increased risk for these sequelae. Many reinfections reflect persistence which likely plays an important role in pathogenesis. The major outer membrane protein is considered to be the immunodominant protein of CT. However, the discovery of open reading frames predicted to encode a nine-member polymorphic membrane protein (Prop) gene (pmp) family in the recently published genome sequence of CT serovar D suggest that these Props may also be important in clalamydial biology. Further, CT contains a partial tryptophan biosynthesis operon (trpR, trpA, trpB) not found in a CT mouse strain (MoPn) or other species of Chlamydia. Tryptophan is essential for chlamydial replication, and tryptophan depletion in vitro results in cblamydial persistence. Our hypothesis is that the prop and tryptophan genes may undergo selection that results in differential expression or activity of these proteins that: 1) consequently determine active or persistent infection; and 2) are significantly involved in pathogenesis as an outcome of persistence or outcome of other factors. By analyzing the genetic profile of prototype and serial recurrent and persistent CT STD patient strains and by correlating these data with epidemiologic and clinical findings, we hope to identify the genes, genetic/protein variation and evolution of this variation in the organism, and how these are linked to persistence and patbogenesis. Thus, this grant will answer broad questions about the genetic and protein basis for persistence and for pathogenesis, and provide important research tools including a Database and DNA microarray that will be of long term benefit to investigators in the field of Chlamydia. The Specific Aims for this grant are to: 1) Sequence the nine pmps, and trpR, trpA, and trpB genes for the 19 prototype serovars of CT and create a DNA microarray for these genes and ompA to differentiate strains of CT, and for use in Aim 2; and 2) Identify polymorphisms in and protein expression of the nine props, specific tryptophan operon genes, and other constitutively expressed genes among serial cervical samples from patients with persistent versus non-persistent CT STDs; correlate the genetic and protein expression profiles of these serial samples with epidemiologic and clinical findings.

沙眼衣原体（CT）是发达的性传播疾病（STD）的主要原因世界。 CT感染及其骨盆炎性疾病，异位妊娠和不育的后遗症是负责美国这些感染估计25亿美元的估计约80％。更远，多达50％的女性被恢复，这些后遗症的风险增加。许多恢复反映了持久性可能在发病机理中起重要作用。主要的外膜蛋白是被认为是CT的免疫主导蛋白。但是，发现开放阅读框的发现在最近发表的 CT血清d的基因组序列表明，这些道具在氯化物生物学中也可能很重要。此外，CT包含一个部分色氨酸生物合成操纵子（TRPR，TRPA，TRPB）（MOPN）或其他衣原体。色氨酸对于衣原体复制和色氨酸至关重要体外耗尽会导致cblamydial持久性。我们的假设是道具和色氨酸基因可能进行选择，从而导致这些蛋白质的差异表达或活性：1）因此确定主动感染或持续感染； 2）与发病机理显着有关其他因素的持久性或结果。通过分析原型和串行复发的遗传特征以及持续的CT性病患者菌株，并通过将这些数据与流行病学和临床发现相关联，我们希望鉴定生物体中这种变异的基因，遗传/蛋白质变异和演变，以及它们是如何的与持久性和par症有关。因此，该赠款将回答有关遗传和持久性和发病机理的蛋白质基础，并提供重要的研究工具，包括数据库 DNA微阵列将对衣原体领域的研究人员长期受益。该赠款的具体目的是：1）序列九个PMP，以及trpr，trpa和trpb基因 19 CT的原型血清射手，并为这些基因创建DNA微阵列，并为OMPA区分菌株 CT，用于AIM 2； 2）确定九种道具的多态性和蛋白质表达，特异性色氨酸操纵子基因和其他组成型表达的基因在患者的系列宫颈样品中具有持久性与非持久性CT性STD；将这些的遗传和蛋白质表达谱相关联具有流行病学和临床发现的系列样品。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Predicting phenotype and emerging strains among Chlamydia trachomatis infections.

DOI：
10.3201/eid1509.090272
发表时间：
2009-09
期刊：
Emerging infectious diseases
影响因子：
11.8
作者：
Dean D;Bruno WJ;Wan R;Gomes JP;Devignot S;Mehari T;de Vries HJ;Morré SA;Myers G;Read TD;Spratt BG
通讯作者：
Spratt BG

Association of carotid plaque Lp-PLA(2) with macrophages and Chlamydia pneumoniae infection among patients at risk for stroke.