PROJECT SUMMARY The human skin microbiome plays a critical role in maintaining skin health, and dysbiosis of this system is associated with increased incidence of disease. Probiotics purported to contain beneficial bacteria are increasingly being used in skincare products, but the rationale for their application to the skin surface is lacking. To develop effective probiotics, an improved understanding of the composition, function, and interactions of the human skin microbiome is needed. The most common class of bacteria that comprises the healthy skin microbiome is coagulase-negative staphylococci, but their role in maintaining skin health is not well understood. Our preliminary data indicate that a common skin commensal, Staphylococcus hominis, produces a bacteriocin that exhibits antimicrobial activity against other commensal skin bacteria. The first goal of this project is to elucidate the structure and biosynthetic mechanisms of the bacteriocin. Additionally, we aim to investigate the role of S. hominis bacteriocins and other S. hominis metabolites in mediating interactions between microbes and eliciting host responses. Overall, this study aims to advance our understanding of the chemical and biological interactions between the commensal bacteria and host cells, with the potential to inform the future development of probiotics for maintaining skin health. The fellowship training plan, which will be carried out in a graduate program that emphasizes research in natural products and integrative medicine, will augment the trainee’s skills in mass spectrometry metabolomics, natural products isolation and structure elucidation, and will provide her an opportunity to gain new skills in microbiology and microbiome research. The training plan has been tailored to the specific planned career trajectory of the trainee, which is to become an independent researcher and secure an academic position. The training will be conducted under the guidance of Dr. Nadja Cech (sponsor) and Dr. Alexander Horswill (co-sponsor), both of whom have extensive experience mentoring students who have gone on to tenured professorships. The project aligns with the mission of the National Center for Complementary and Integrative Health (NCCIH), contributing to public health by providing insights that could inform the development of skin probiotics.

PROJECT NARRATIVE Consumers often seek to address skin conditions using probiotics, but the safety and efficacy of these products are undetermined. This study aims to elucidate the mechanisms by which commensal bacteria that comprise the skin microbiome interact with each other and with host cells to maintain skin health. The findings of this study are expected to inform future evaluations of the safety and efficacy of probiotics.