Defining the role of cobamides in skin microbiome dynamics

项目摘要 人类皮肤微生物组是一个复杂而独特的微生物群群落，其对人类皮肤和皮肤都有贡献。 健康和疾病。然而，皮肤内发生的基本生物和生态相互作用 维持微生物组结构、稳定性和功能以及整体皮肤健康的微生物群落， 未知通常，这些相互作用由微生物代谢物介导。钴酰胺是微生物 维生素B12家族辅因子的代谢物，对于许多细菌的代谢以及 人类，但它们只由一小部分原核生物合成。初步研究表明，宿主- 棒状杆菌属内的相关物种，一个占主导地位的皮肤分类群，是丰富的从头 钴酰胺生物合成途径，包括几个人类皮肤相关物种。一个新兴的 文献表明，微生物之间的钴酰胺共享在介导微生物 社区动态然而，微生物来源的钴酰胺在皮肤表面的作用从未被证实。 研究了因此，本提案的总体目标是描述钴胺的调控机制 由个体皮肤微生物和社区内产生和使用。这将是完成 通过两个相关的目标。首先，皮肤外用和钴酰胺的生物合成的特征在于： 分析皮肤宏基因组数据，并通过使用体外微生物和化学方法进行验证， 方法。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 使用活的人类皮肤模型在体外和离体使用合成皮肤微生物群落。完成 这些目标将确定钴酰胺在皮肤微生物组中以前未探索的作用，这将增加 我们对皮肤微生物组在人体中作用的基本生物学过程的理解 健康这些研究将提出一种新的治疗靶点，用于用维生素D改造微生物组。 生产益生菌，并将通过微量营养素共享为微生物组调节奠定基础。的 通过F31 NRSA提供的支持将进一步促进申请人在充满活力的环境中的科学培训。 威斯康星大学麦迪逊分校的研究环境，并将提供必要的资源， 推进她的职业生涯，成为一个独立的科学家和专家领域的 微生物研究

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.