C. trachomatis genomics, strain typing, and evolution

沙眼衣原体基因组学、菌株分型和进化

基本信息

批准号：
7408642
负责人：
DEBORAH Anne DEAN
金额：
$ 53.36万
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：
2004
资助国家：
美国
起止时间：
2004-04-01 至 2011-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7408642
关键词：
Address Adolescent Adult Amino Acids Apache Indians Arthritis Basic Science Bioinformatics Biology Blindness CPA factor Chlamydia Chlamydia Infections Chlamydia trachomatis Chlamydia trachomatis omp1 protein Chlamydiaceae Chlamydiales Chlamydophila Chlamydophila pneumoniae Chlamydophila psittaci Clinical Collection Conjunctivitis Cytotoxin DNA Data Databases Development Disease Disease Outcome Distant Educational workshop Epidemiologic Studies Evolution Family Gene Proteins Genes Genetic Genetic Determinism Genetic Drift Genetic Polymorphism Genital system Genome Genomics Genotype Goals Grant Human Immune response Infant Laboratories Learning Link Locales Membrane Proteins Methods Molecular Mutation Nucleotides Numbers Operon Organism Outcome Pathogenesis Pathogenicity Patients Phylogeny Pneumonia Population Property Proteins Publishing Purpose Range Reading Recurrent disease Research Research Personnel Research Proposals Scheme Screening procedure Serotyping Sexually Transmitted Diseases Shotguns Societies Specificity Statistical Models Surveys Time Tissues Today Trachoma Tryptophan Type III Secretion System Pathway United States National Institutes of Health Variant Virulence base comparative data collection methodology design functional genomics genome sequencing major outer membrane protein member pathogen porin programs research study tissue tropism tool

项目摘要

DESCRIPTION (provided by applicant): Chlamydia trachomatis (CT) is the leading cause of preventable blindness (trachoma) and sexually transmitted diseases (STD) worldwide. While much has been learned about human chlamydial infections in the last decades, we are still lacking a complete understanding of the pathogenesis of CT diseases, and do not have an appropriate tool for precisely typing CT strains both for molecular epidemiologic and basic research studies. The major outer membrane protein (MOMP) of CT is an immunodominant protein and the primary target for serotyping, and hence strain typing along with the ompA gene, which encodes MOMP. Yet, MOMP does not fully reflect the phylogeny of the organism or distinguish strains by biologic or phenotypic properties. Other genes/proteins that may contribute to phylogeny, or these properties include the inter-genic region (IGR), polymorphic membrane proteins (Pmps), cytotoxin genes in the replication termination region (RTR) or "plasticity zone", partial tryptophan operon proteins (TrpB/A), Type III secretion system proteins, chlamydial protease- or proteasome-like activity factor (CPAF), and the porin protein, PorB. Further, the majority of research on CT has used laboratory-adapted strains that may not reflect current clinical isolates that are responsible for the myriad of CT diseases described today. Our goal is to advance the genetic discovery initiated by the CT genome sequences of serovars D and L2 and other genomes of the family Chlamydiaceae by providing genome sequences of six of the 13 remaining reference serovars along with genomes of recent clinical isolates to advance our understanding of CT tissue tropism, virulence, disease pathogenesis, and evolution. Within the context of our Specific Aims, we will develop and make publicly available the data and research tools described: 1) Sequence six genomes of the remaining 13 reference serovars of CT and four genomes of selected recent clinical isolates (see #2), and develop a multi-locus sequence typing (MLST) scheme for global epidemiologic studies; MLST screening of the seven remaining reference serovars and -500 isolates from CT STD and trachoma populations worldwide will fine-tune the MLST and identify unique clinical isolates for additional genome sequencing; 2) Develop a Chlamydia GeneChip for rapid, robust genotyping of CT based on genome data and MLST findings; and 3) Develop a strain identification database to address specific research questions related to unraveling the association between genetic determinants and tissue tropism, virulence, and disease outcome in addition to the evolution of the organism and how new strain types might evolve over time.

描述（由申请人提供）：沙眼衣原体（CT）是全球可预防失明（沙眼）和性传播疾病（STD）的主要原因。尽管过去几十年来已经了解了人类衣原体感染，但我们仍然缺乏对CT疾病的发病机理的完全了解，并且没有适当的工具来精确地键入分子流行病学和基础研究的CT菌株。 CT的主要外膜蛋白（MOMP）是一种免疫主导蛋白，是血清分型的主要靶标，因此与编码MOMP的OMPA基因一起拼接。但是，MOMP并未完全反映生物体的系统发育，也不能通过生物或表型特性区分菌株。可能导致系统发育的其他基因/蛋白质，或这些特性包括复制终止区（RTR）区域（RTR）或“可塑性区域”中的细胞毒素基因的多态膜蛋白（PMP）或部分蛋白质蛋白（TRPB/trpb/tym ote ote ote ote ote ote ote ote ote otty otty otty rote蛋白，活性因子（CPAF）和孔蛋白蛋白，PORB。此外，关于CT的大多数研究都使用了实验室适应的菌株，这些菌株可能无法反映当前临床分离株，这些分离株造成了今天所描述的无数CT疾病。我们的目标是通过提供13个剩余参考血清的六个基因组序列以及最近的临床隔离基因组中的基因组序列以及我们对CT组织的特性，病毒性，病毒性，病毒性，疾病的基因，疾病的基础，疾病的基因，和疾病的建筑，和疾病的基因组的理解，通过提供血清衣原体科的CT基因组序列以及家族衣原体科的其他基因组引发的遗传发现。在我们的特定目标的背景下，我们将开发并公开获得所描述的数据和研究工具：1）序列的六个基因组，其余13个CT参考血清的CT和四个基因组和四个近期临床分离株的四个基因组（请参见＃2），并开发多层次序列序列键入（MLST）全球流行病学研究方案； MLST筛选全球CT STD和三方种群中剩余的七个参考血清群和-500个分离株将微调MLST并确定独特的临床分离株以进行其他基因组测序。 2）开发一种基于基因组数据和MLST发现的CT快速，稳健基因分型的衣原体构造； 3）开发一个菌株识别数据库，以解决与揭示遗传决定因素与组织对流，毒力和疾病结果之间关联的特定研究问题，此外还有生物体的演变以及新的菌株类型如何随着时间的流逝而发展。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Identification of novel single nucleotide polymorphisms in inflammatory genes as risk factors associated with trachomatous trichiasis.

DOI：
10.1371/journal.pone.0003600
发表时间：
2008
期刊：
PLOS ONE
影响因子：
3.7
作者：
Atik, Berna;Skwor, Troy A.;Kandel, Ram Prasad;Sharma, Bassant;Adhikari, Him Kant;Steiner, Lori;Erlich, Henry;Dean, Deborah
通讯作者：
Dean, Deborah

Chlamydia trachomatis today: treatment, detection, immunogenetics and the need for a greater global understanding of chlamydial disease pathogenesis.

当今的沙眼衣原体：治疗、检测、免疫遗传学以及全球对衣原体疾病发病机制有更深入了解的必要性。