Understanding Intraspecific Diversity of Gardnerella vaginalis in the Vaginal Microbiome

项目摘要 阴道加德纳菌与细菌性阴道病（BV）和早产（PTB）风险有关， 但在识别、治疗和预防风险方面几乎没有成功。越来越多的G。迷走神经变异有 与这些结果和相关的致病行为之间存在差异。这些差异 已被链接到巨大的系统发育和表型多样性在命名的物种，G。流浪汉， 已经被认为代表了多达13个基因组物种。为了最终了解，防止， 和治疗致病性结果，我们必须定义一个一致的和可靠的方法来识别G。阴道毛 变体。我们已经证明了鉴定六个亚种G的存在和丰度的能力。 在鸟枪宏基因组测序数据中，这是了解如何在基因组中表达vaginoclaves进化枝的重要一步。 这些分支可以塑造它们的微生物群落。初步证据表明， 与每个进化枝相关的群落特征。我们假设G.各分支的不同之处在于 总体相对转录速率、致病相关基因转录量以及G. 早产中的迷走神经转录物在进化枝之间变化。我们还假设G.不定枝不同 在与塑造微生物群落和宿主健康的能力有关的表型中。我们将使用配对 宏基因组和元转录组测序数据来描述G.迷走神经分支转录 怀孕和早产。我们还将使用体外试验来评估上皮粘附、生物膜形成， 和对乳杆菌属的竞争性生长。进化枝成功实现这些目标将 表明6个G之间存在临床相关变异。不定枝因此，这些目标代表了 独特的多学科方法，系统地了解G。流浪多样性，这是必要的， 用于确定BV和PTB等疾病的健康风险，并制定成功的干预策略。 这些目标还将提供计算和技术技能方面的培训， 研究人员能够弥合学科，以解决复杂的问题，在生物医学。

Project Summary Gardnerella vaginalis has been associated with bacterial vaginosis (BV) and preterm birth (PTB) risk, but with little success in being able to identify, treat, and prevent risk. Increasingly, G. vaginalis variants have been differentially associated with these outcomes and associated pathogenic behaviors. These differences have been linked to vast phylogenetic and phenotypic diversity across the named species, G. vaginalis, which has been suggested to represent as many as 13 genomic species. In order to eventually understand, prevent, and treat pathogenic outcomes, we must define a consistent and reliable method to identify G. vaginalis variants. We have demonstrated the ability to identify the presence and abundance of six subspecies G. vaginalis clades in shotgun metagenomic sequencing data, which is an important step in understanding how these clades may shape their microbial communities. Preliminary evidence suggests potential differences in community signatures associated with each clade. We hypothesize six subspecies G. vaginalis clades differ in overall relative transcription rates, transcription of genes related to pathogenicity, and that fold increases of G. vaginalis transcripts in preterm birth vary among the clades. We also hypothesize that G. vaginalis clades differ in phenotypes that relate to the ability to shape the microbial community and host health. We will use paired metagenomic and metatranscriptomic sequencing data to describe G. vaginalis clade transcription in pregnancy and preterm birth. We will also use in vitro assays to assess epithelial adhesion, biofilm formation, and competitive growth against Lactobacillus spp. of the clades. Successful completion of these aims will demonstrate clinically relevant variation among six G. vaginalis clades. Therefore, these aims represent a unique multidisciplinary approach to the systematic understanding of G. vaginalis diversity, which is necessary for identifying health risks in conditions such as BV and PTB, and targeting successful intervention strategies. These aims will also provide training in both computational and technical skills to foster an independent researcher capable of bridging disciplines to solve complex problems in biomedicine.