(492b) Understanding and Engineering the Metabolic Environment of a Healthy Skin Microbiome

The skin is the largest organ and the first line of protection against external factors. The skin environment is generally cool, acidic, and dry with inter- and intra-personal variation in pH, temperature, moisture content, elasticity and metabolite profiles. Different skin sites are colonized by diverse bacteria from Actinobacteria, Firmicutes, Proteobacteria and Bacteroidetes and fungi from Ascomycota and Basidiomycota. Some of these organisms are beneficial and contribute to protective properties of the skin. Skin commensal bacteria influence wound healing and infection by pathogens through direct antimicrobial activity and signaling host cells to boost innate and adaptive immune responses. To study these interactions and harness the protective power of commensal skin organisms, we are developing in vitro systems to monitor metabolic and immune responses of microbial skin isolates and skin cell cultures. Metabolic predictions of microbial growth states indicate that the skin pathogens are highly complementary with commensal isolates, suggesting an ecological mechanism for colonization. Staphylococcus aureus, a pathogenic skin organism, produces a small molecule which kills cultured skin models, while Staphylococcus epidermidis, a commensal isolate, protects cultured skin cells from pathogen growth. Further, in one-on-one interaction assays S. epidermidis inhibits the growth of S. aureus and other pathogens. Towards understanding the physical and chemical interactions important for the skin microbiome, we have developed reporter strains for skin isolates and have imaged infection dynamics using confocal and time-lapse microscopy. Collectively, our experiments suggest that commensal strains can have direct antimicrobial activity against pathogens and can activate host immune responses to further inhibit growth of pathogens. Improved understanding of these systems will allow us to examine interactions between resident microorganisms of the human skin and ultimately enable engineering the metabolic environment of the skin to encourage growth of beneficial microorganisms and enhance human health.