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: 8134990
• 负责人: PATRIK M BAVOIL
• 金额: $ 245.03万
• 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/8134990
• 关键词: Eco; Pathogenomics; Chlamydial; Reproductive; Tract

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存在互惠关系，并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抗引起疾病的入侵性非本土生物体（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，人们对健康和疾病中阴道微生物群落的组成和动态知之甚少。传统的基于培养的方法提供了一个有价值但不完整的人类阴道微生物群的图片。在这项研究中，我们将联合收割机平行测序技术与16 S rRNA基因序列的非培养分析相结合，以调查年轻成年人阴道微生物群的物种组成和丰度。沙眼衣原体感染和C.沙眼阳性的女性盆腔炎（PID）患者。此外，我们还将建立社区的动态，一个在治疗后一年或一年以上纵向抽样的妇女亚组。在这些女性中，我们将使用社区转录组学来识别阴道微生物群落表达的基因组。该组合数据将提供衣原体感染期间和之后的阴道微生物群动态的独特视图（即，对感染（直接或间接）的反应所触发的代谢途径的详细描述]，并将进一步完善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。感染豚鼠的雌性豚鼠。了解和表征阴道微生物群的重要性将大大有助于开发基于合理性和科学合理原则的新方法，以在治疗的同时操纵阴道微生物群。 200多个C. trachomatis或C.将使用454焦磷酸测序对从这些生物样品中分离的豚鼠进行测序。这些序列将代表一个无与伦比的资源，将与研究界共享。序列数据将与阴道微生物群和该联盟的两个项目下表征的表型进行相关分析。