Nutritional landscape and community interactions in the vaginal microbiome

项目总结 阴道是一个严酷的、多菌的生态系统，具有积极的免疫反应，富含 宫颈阴道粘液，并有一个强大的微生物区系。细菌在这种环境中的持久性要求 生物体适应养分供应变化并与其他生物相互作用的能力 微生物区系。阴道微生物区系按五种群落状态类型分类，其中状态类型I、II、III和 V类以乳杆菌类为主，而IV类群落以群落数量增加为标志 生物多样性，大致称为“非生物多样性”。我们对阴道健康的定义正在演变；然而， 我们对影响社区结构和功能的基本原则的理解，以及 个体微生物在群落中的稳定性尚不清楚。确定哪些交互作用有助于 在这个动态的环境中坚持是具有挑战性的，因为这些因素本质上是多因素的。在这里，我们 提出跨学科的方法来了解阴道的微生物生态，并推动我们的 阴道健康的基本知识。我们的目标是确定阴道内的营养景观如何 影响微生物群落的组装、结构和相互作用，共同促进持久性 殖民主义。我们将定义金属在阴道内的可用性，并使用这些数据来了解如何 细菌群落的环境、形态、组成和功能的变化。由此，我们将确定 生物可利用金属对社区成员的持久性和扩张性的不同重要性。我们会 研究金属离子动态平衡的机制并确定它们对细胞代谢的影响， 微生物群落内部的合作和竞争。我们将在二氧化硅模型中进行开发并验证 阴道微生物区系成员之间代谢相互作用的机制及其作用 社区协同中的互动。我们的目标是定义阴道生态如何推动社区互动和 在这个复杂的环境中促进殖民的相声。这些发现有可能将金属 体内可利用性、细胞代谢和微生物群落结构。总而言之，这项提案将使用 合成阴道群落，以描述推动 阴道粘膜中的微生物相互作用。这些发现将提供对生态环境的更好理解 影响阴道群落组成、稳定性和相互作用的因素。这项工作将推动我们的 基础知识和确定相关的治疗目标，可有助于促进 保持阴道健康。

PROJECT SUMMARY The vaginal tract is a harsh, polymicrobial ecosystem that has an active immune response, is rich in cervicovaginal mucins, and has a robust microbiota. Bacterial persistence within this environment requires the ability of organisms to adapt to changes in nutrient availability and to interact with the other members of the microbiota. The vaginal microbiota is classified by five community state types, in which state types I, II, III, and V are dominated by Lactobacillus species, while community state type IV is marked by increased community diversity and is loosely termed “dysbiotic”. Our definition of what constitutes vaginal health is evolving; however, our understanding of the fundamental principles that impact community structure and function, and the role individual microbes have in community stability is unknown. Determining the interactions that contribute to persistence within this dynamic environment is challenging, as these are multifactorial in nature. Here, we propose interdisciplinary approaches to understand the microbial ecology of the vaginal tract and advance our basic knowledge of vaginal health. Our objective is to determine how the nutritional landscape within the vagina impacts microbial community assembly, structure, and interactions, that together, contribute to persistent colonization. We will define metal availability within the vaginal tract and use these data to understand how changes in the environment shape composition and function of bacterial communities. From this, we will identify differential importance of bioavailable metals for persistence and expansion of community members. We will investigate the mechanisms of metal ion homeostasis and determine their impact on cellular metabolism, cooperation, and competition within microbial communities. We will develop in silica models and validate mechanisms of metabolic interaction between members of the vaginal microbiota and determine the role of these interactions in community synergy. Our goal is to define how vaginal ecology drives community interactions and crosstalk to promote colonization in this complex environment. These findings have the potential to link metal availability, cellular metabolism, and microbial community structure in vivo. Together, this proposal will use synthetic vaginal communities to profile the genetic, physiological, and ecological mechanisms that drive microbial interactions in the vaginal mucosa. These findings will provide a better understanding of the ecological factors that contribute to vaginal community composition, stability, and interactions. This work will advance our fundamental knowledge and identify relevant therapeutic targets that could serve to promote efforts in maintaining vaginal health.