Nutritional landscape and community interactions in the vaginal microbiome

项目摘要 阴道是一个严酷的多微生物生态系统，具有活跃的免疫反应，富含 宫颈阴道粘蛋白，并具有强大的微生物群。细菌在这种环境中的持久性需要 生物体适应养分供应变化的能力，以及与环境中其他成员相互作用的能力。 微生物群阴道微生物群按五种群落状态类型分类，其中状态类型I、II、III和III分别为： V型以乳杆菌属物种为主，而IV型以增加的群落为特征 多样性，并被松散地称为“生态失调”。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是未知的。确定有助于 在这一动态环境中的持久性具有挑战性，因为这些问题本质上是多因素的。这里我们 提出跨学科的方法来了解阴道的微生物生态学，并推进我们的 阴道健康的基本知识。我们的目标是确定阴道内的营养状况 影响微生物群落的组装，结构和相互作用，共同促进持久的 殖民化我们将定义阴道内的金属可用性，并使用这些数据来了解如何 环境的变化塑造了细菌群落的组成和功能。由此，我们将确定 生物可利用的金属对于社区成员的持久性和扩展的不同重要性。我们将 研究金属离子稳态的机制，并确定它们对细胞代谢的影响， 微生物群落内的竞争和合作。我们将在二氧化硅模型中开发并验证 阴道微生物群成员之间的代谢相互作用的机制，并确定这些微生物群的作用。 社区协同作用的互动。我们的目标是确定阴道生态学如何驱动社区互动， 在这个复杂的环境中促进殖民化。这些发现有可能将金属 可用性、细胞代谢和体内微生物群落结构。这项提案将利用 合成阴道群落，以分析遗传，生理和生态机制， 阴道粘膜中的微生物相互作用。这些发现将使人们更好地了解 有助于阴道群落组成、稳定性和相互作用的因素。这项工作将促进我们的 基本知识，并确定相关的治疗目标，可以促进努力， 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.