Understanding Intraspecific Diversity of Gardnerella vaginalis in the Vaginal Microbiome

了解阴道微生物组中阴道加德纳菌的种内多样性

• 批准号: 10328251
• 负责人: Hanna L Berman
• 金额: $ 3.85万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10328251
• 关键词: 16S ribosomal RNA sequencing; Adhesions; Bacterial Vaginosis; Behavior; Biological Assay; Categories; Cervical; Classification; Communities; Complex; Custom; Data; Databases; Discipline; Epithelial; Epithelial Cells; Fostering; Gardnerella vaginalis; Gene Expression; Genes; Genetic Transcription; Genomics; Goals; Growth; Gynecologic; Health; In Vitro; Intervention; Lactobacillus; Link; Measures; Mediating; Metagenomics; Methods; Microbe; Microbial Biofilms; Modeling; Names; Neonatal Mortality; Outcome; Pathogenicity; Phenotype; Phylogenetic Analysis; Population; Pregnancy; Pregnant Women; Premature Birth; Prevalence; Research; Research Personnel; Risk; Risk Factors; Sexually Transmitted Diseases; Shapes; Shotguns; Swab; System; Taxon; Technical Expertise; Term Birth; Training; Transcript; Vagina; Variant; base; clinically relevant; cohort; differential expression; direct application; disease diagnosis; improved; in vitro Assay; interdisciplinary approach; metagenomic sequencing; metatranscriptomics; microbial; microbial community; microbial host; monolayer; multiple omics; novel; obstetric outcomes; prevent; success; successful intervention; vaginal microbiome; vaginal microbiota; vaginal mucosa

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.

项目摘要 阴道加德纳（Gardnerella Vaginalis）与细菌性阴道病（BV）和早产（PTB）风险有关， 但是几乎没有成功，无法识别，治疗和预防风险。越来越多的阴道变体具有 与这些结果和相关的致病行为有所不同。这些差异 已与命名的物种G. g。g。g。 有人建议代表多达13种基因组物种。为了最终理解，防止， 并治疗致病结果，我们必须定义一种一致且可靠的方法来识别阴道 变体。我们已经证明了识别六个亚种的存在和丰度的能力。 shot弹枪宏基因组测序数据中的阴道进化枝，这是理解如何 这些进化枝可能会塑造其微生物群落。初步证据表明 每个进化枝相关的社区签名。我们假设六个亚种G.阴道进化枝不同 总体相对转录率，与致病性相关的基因的转录以及G的倍数增加。 在进化枝中，早产中的阴道转录本不同。我们还假设V.阴道枝不同 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 元基因组和元转录组测序数据，描述了阴道的G. o. ot 怀孕和早产。我们还将使用体外测定法评估上皮粘附，生物膜形成， 和针对乳酸杆菌的竞争增长。进化枝。这些目标的成功完成将 证明了六个阴道螺旋藻在临床上相关的变异。因此，这些目标代表 独特的多学科方法来系统地了解G.阴道多样性，这是必要的 在BV和PTB等条件下确定健康风险，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的培训，以培养独立 能够弥合学科以解决生物医学中复杂问题的研究人员。