Nutritional landscape and community interactions in the vaginal microbiome

项目总结

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.