Eco-Pathogenomics of Chlamydial Reproductive Tract Infection (EPCRTI)

描述（由申请人提供）：与人类阴道相关的微生物群与人类宿主存在互惠关系，被认为在女性生殖健康中发挥重要作用。阴道微生物群落构成了抵御侵入性非本地致病生物（如性传播的沙眼衣原体）感染的第一道防线。尽管它们很重要，但令人惊讶的是，人们对阴道微生物群落在健康和疾病中的组成和动态知之甚少。传统的基于培养的方法提供了人类阴道微生物群的有价值但不完整的图片。在这项研究中，我们将结合大规模平行测序技术和16S rRNA基因序列的培养独立分析，调查年轻沙眼衣原体感染和沙眼衣原体-晚期盆腔炎（PID）女性阴道微生物群的种类组成和丰度。此外，我们将在治疗后一年或更长时间内对妇女进行纵向抽样，建立社区动态。在这些女性中，我们将使用群落转录组学来鉴定阴道微生物群落表达的基因套件。这些综合数据将为衣原体感染期间和之后的阴道微生物群动态提供一个独特的视角（即，对感染（直接或间接）引起的代谢途径的详细描述），并将进一步推动我们的衣原体感染和再感染模型。由于使用人类作为研究对象的局限性，豚鼠被用作衣原体感染的动物模型。同样，我们将描述健康和C. caviae感染的雌性豚鼠阴道微生物群随时间的变化。理解和描述阴道微生物群的重要性将极大地促进基于基本原理和科学合理原则的新方法的发展，从而在治疗的同时控制阴道微生物群。利用454焦磷酸测序技术对从这些生物样本中分离的200多株沙眼衣原体或鱼穴衣原体进行基因组测序。这些序列将代表一个无与伦比的资源，将与研究界共享。该序列数据将与该联盟两个项目下阴道微生物群和表型特征的相关性进行分析。

DESCRIPTION (provided by applicant): The microbiota associated with the human vagina exists in a mutualistic relationship with the human host and is believed to play an important role in women's reproductive health. The vaginal microbial communities constitute the first line of defense against infection by invasive non-indigenous organisms that cause disease, such as the sexually transmitted Chlamydia trachomatis. Despite their importance, surprisingly little is known about the composition and dynamics of vaginal microbial communities in health and disease. Traditional cultivation-based methods have provided a valuable but incomplete picture of the human vaginal microbiota. In this study, we will combine massively-parallel sequencing technology with the culture-independent analysis of the 16S rRNA gene sequence to survey the vaginal microbiota species composition and abundance in young adults with C. trachomatis infection and C. trachomatis-pos\t\\/e women with pelvic inflammatory disease (PID). In addition, we will establish the dynamics of the community a subgroup of women sampled longitudinally over one year or more after treatment. In each of these women, we will use community transcriptomics to identify the suite of genes expressed by the vaginal microbial community. This combined data will afford a unique view of the vaginal microbiota dynamics during and after Chlamydial infection (i.e., a detailed picture of the metabolic pathways triggered in response to the infections (directly or indirectly)], and will further our model of Chlamydial infection and re-infection. Because of limitations in using humans as research subjects, guinea pigs are used as animal model for Chlamydial infections. Similarly, we will characterize the vaginal microbiota in healthy and C. caviae-infected female guinea pigs over time. Understand and characterizing the importance of the vaginal microbiota will contribute greatly to the development of new approaches based on rationale and scientifically sound principles to manipulate the vaginal microbiota in parallel to treatments. The genome of more than 200 C. trachomatis or C. caviae-isolated from these biological samples will be sequenced using 454 pyrosequencing. These sequences will represent an unparalleled resource that will be shared with the research community. The sequence data will be analyzed in correlation with the vaginal microbiota and the phenotypes characterized under the two projects of this consortium. PROJECT 1: ECOLOGY OF THE VAGINA UPON CHLAMYDIAL INFECTIONS (RAVEL, J) PROJECT 1 DESCRIPTION (provided by applicant): The microbiota associated with the human vagina exists in a mutualistic relationship with the human host and is believed to play an important role in women's reproductive health. The vaginal microbial communities constitute the first line of defense against infection by invasive non-indigenous organisms that cause disease, such as the sexually transmitted Chlamydia trachomatis. Despite their importance, surprisingly little is known about the composition and dynamics of vaginal microbial communities in health and disease. Traditional cultivation-based methods have provided a valuable but incomplete picture of the human vaginal microbiota. In this study, we will combine massively-parallel sequencing technology with the culture-independent analysis of the 16S rRNA gene sequence to survey the vaginal microbiota species composition and abundance in young adults with C. trachomatis infection and C. trachomatis-pos\t\\/e women with pelvic inflammatory disease (PID). In addition, we will establish the dynamics of the community a subgroup of women sampled longitudinally over one year or more after treatment. In each of these women, we will use community transcriptomics to identify the suite of genes expressed by the vaginal microbial community. This combined data will afford a unique view of the vaginal microbiota dynamics during and after Chlamydial infection (i.e., a detailed picture of the metabolic pathways triggered in response to the infections (directly or indirectly)], and will further our model of Chlamydial infection and re-infection. Because of limitations in using humans as research subjects, guinea pigs are used as animal model for Chlamydial infections. Similarly, we will characterize the vaginal microbiota in healthy and C. caviae-infected female guinea pigs over time. Understand and characterizing the importance of the vaginal microbiota will contribute greatly to the development of new approaches based on rationale and scientifically sound principles to manipulate the vaginal microbiota in parallel to treatments. The genome of more than 200 C. trachomatis or C. caviae-isolated from these biological samples will be sequenced using 454 pyrosequencing. These sequences will represent an unparalleled resource that will be shared with the research community. The sequence data will be analyzed in correlation with the vaginal microbiota and the phenotypes characterized under the two projects of this consortium.