Eco-Pathogenomics of Chlamydial Reproductive Tract Infection (EPCRTI)

衣原体生殖道感染的生态病理基因组学 (EPCRTI)

• 批准号: 8527679
• 负责人: PATRIK M BAVOIL
• 金额: $ 243.63万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-21 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8527679
• 关键词: Aftercare; Animal Model; Biological; Cavia; Chlamydia Infections; Chlamydia trachomatis; Communities; Data; Development; Disease; Female; Genes; Genome; Health; Human; Infection; Infertility; Metabolic Pathway; Methods; Microbe; Modeling; Organism; Pelvic Inflammatory Disease; Phenotype; Play; Process; Reproductive Health; Reproductive Tract Infections; Research; Research Subjects; Resources; Risk; Role; Sampling; Subgroup; Surveys; Technology; Time; Vagina; Woman; base; microbial community; novel strategies; pathogen; pyrosequencing; rRNA Genes; response; sexually active; sound; transcriptomics; young adult

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.

与人类阴道相关的微生物群与人类宿主之间存在着一种互惠互利的关系，并被认为在妇女的生殖健康中发挥着重要作用。阴道微生物群落构成了抵御入侵的非本土生物感染的第一道防线，这些非本土生物会导致疾病，例如性传播的沙眼衣原体。 尽管它们很重要，但令人惊讶的是，人们对阴道微生物群落的组成和动态在健康和疾病中的作用知之甚少。传统的基于培养的方法提供了一幅有价值但不完整的人类阴道微生物区系的图景。在这项研究中，我们将结合大规模平行测序技术和16S rRNA基因序列的非培养分析来调查沙眼衣原体感染的青壮年和患有盆腔炎(PID)的沙眼衣原体感染妇女的阴道微生物区系组成和丰度。此外，我们将建立社区的动态，对治疗后一年或更长时间的妇女进行纵向抽样。在这些女性中，我们将使用社区转录组学来确定阴道微生物群落表达的一套基因。这些综合数据将提供衣原体感染期间和感染后阴道微生物区系动态的独特视角(即，(直接或间接)响应感染而触发的代谢途径的详细图像)，并将进一步发展我们的衣原体感染和再感染模型。由于以人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，随着时间的推移，我们将描述健康和感染豚鼠球虫的雌性豚鼠的阴道微生物区系。了解和确定阴道微生物区系的重要性将极大地有助于开发基于理论基础和科学合理的原则的新方法，以便在治疗的同时操纵阴道微生物区系。 从这些生物样本中分离出的200多种沙眼衣原体或豚鼠衣原体的基因组将使用454焦磷酸测序进行测序。这些序列将代表一个无与伦比的资源，将与研究社区共享。序列数据将与阴道微生物区系和该联盟两个项目下表征的表型相关联地进行分析。