Defining the role of cobamides in skin microbiome dynamics

项目总结 人类皮肤微生物群是一个复杂而独特的微生物群落，对人类和 健康和疾病。然而，发生在皮肤内的基本生物和生态相互作用 微生物群落维持微生物群落的结构、稳定性和功能，以及整体皮肤健康， 未知。通常，这些相互作用是由微生物代谢物调节的。可巴胺，这是微生物 维生素B12家族的代谢物，是许多细菌新陈代谢所必需的 人类，但它们只由一小部分原核生物合成。初步工作表明，宿主- 棒状杆菌属内的相关物种，一个优势的皮肤分类群，为新生而丰富 钴胺的生物合成途径，包括几个与人类皮肤相关的物种。一个新兴的团体 文献表明，微生物间的钴胺共享在微生物调节中起着关键作用 社区动态。然而，微生物衍生的钴酰胺在皮肤表面的作用从来没有 学习。因此，这项提案的总体目标是描述钴酰胺的作用机制 由个体皮肤微生物和社区内生产和使用。这将会实现的 通过两个相互关联的目标。首先，皮肤共生使用和钴酰胺的生物合成将通过 分析皮肤元基因组数据并通过使用体外微生物和化学方法进行验证 接近了。其次，将确定钴酰胺在塑造皮肤微生物群落相互作用中的作用 使用体外和体外合成的皮肤微生物群落，使用活体人类皮肤模型。完成 这些目标将定义钴酰胺在皮肤微生物群中以前未被探索的作用，这将增加 我们对皮肤微生物群在人体中作用的基本生物学过程的理解 健康。这些研究将为设计含有维生素的微生物组提供一个新的治疗靶点。 生产益生菌，并将为通过分享微量营养素进行微生物组调控奠定基础。这个 通过F31 NRSA提供的支持将进一步有助于申请者在充满活力的 威斯康星大学麦迪逊分校的研究环境，将提供必要的资源 推动她的职业生涯，成为一名独立的科学家和领域的专家 微生物组研究。

PROJECT SUMMARY The human skin microbiome is a complex and distinct community of microbiota that contributes to both human health and disease. However, the fundamental biological and ecological interactions that occur within skin microbial communities to maintain microbiome structure, stability, and function, and overall skin health, are unknown. Often, these interactions are mediated by microbial metabolites. Cobamides, which are microbial metabolites of the vitamin B12 family of cofactors, are essential for metabolism in many bacteria as well as humans, but they are only synthesized by a small fraction of prokaryotes. Preliminary work has shown that host- associated species within the Corynebacterium genus, a dominant skin taxon, are enriched for the de novo cobamide biosynthesis pathway, including several human skin-associated species. An emerging body of literature suggests that cobamide sharing between microorganisms plays a key role in mediating microbial community dynamics. However, the role for microbial-derived cobamides at the skin surface has never been studied. Therefore, the overall objective of this proposal is to characterize the mechanisms governing cobamide production and usage by individual skin microorganisms and within communities. This will be accomplished through two related Aims. First, skin commensal use and biosynthesis of cobamides will be characterized by analyzing skin metagenomic data and validated through the use of in vitro microbiological and chemical approaches. Second, the role of cobamides in shaping skin microbial community interactions will be determined using synthetic skin microbial communities both in vitro and ex vivo using a live human skin model. Completion of these aims will define the previously unexplored role of cobamides in the skin microbiome, which will increase our understanding of the fundamental biological processes that underly the skin microbiome’s role in human health. These studies will present a novel therapeutic target for engineering the microbiome with vitamin- producing probiotics and will lay the groundwork for microbiome modulation via micronutrient sharing. The support provided through the F31 NRSA will further contribute to the applicant’s scientific training in the vibrant research environment at the University of Wisconsin-Madison and will provide the necessary resources to advance her professional career towards becoming an independent scientist and expert in the field of microbiome research.