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收效甚微。阴道毛滴虫的变异体越来越多地 与这些结果和相关的致病行为有不同的关联。这些差异 与命名物种阴道革兰氏菌巨大的系统发育和表型多样性有关，这是 已被建议代表多达13个基因组物种。为了最终了解、预防、 和治疗病原学结果，我们必须定义一个一致和可靠的方法来鉴定阴道毛滴虫 变种。我们已经证明了能够识别六个亚种G. 阴道分支在鸟枪式元基因组测序数据中，这是理解如何 这些分支可能会塑造它们的微生物群落。初步证据表明， 与每个分支关联的社区签名。我们推测六个亚种的阴道革兰氏菌在 总相对转录速率、致病相关基因转录和G. 早产的阴道转录本在不同的支系之间存在差异。我们还假设阴道毛滴虫的分支不同 与塑造微生物群落和宿主健康的能力有关的表型。我们将使用配对 描述阴道毛滴虫分支转录的元基因组和后转录测序数据 怀孕和早产。我们还将使用体外试验来评估上皮粘连、生物膜形成、 与乳杆菌的竞争性生长。在支派中。这些目标的成功实现将 展示了6个阴道毛滴虫分支之间的临床相关变异。因此，这些目标代表着 以独特的多学科方法系统地了解阴道毛滴虫的多样性，这是必要的 用于识别BV和肺结核等条件下的健康风险，并针对成功的干预策略。 这些目标还将提供计算和技术技能方面的培训，以培养独立的 研究人员能够跨越学科，解决生物医学中的复杂问题。

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.