Defining the role of cobamides in skin microbiome dynamics

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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.