(492d) Targeted Species Removal in a Model Microbiome Via Phage Lytic Enzymes

Surveying microbiome composition (genomics, metagenomics) and assessing function through metatranscriptomic and metabolomic approaches have transformed our understanding of biodiversity and the roles microbes play in human health. However, new approaches and technologies are needed to develop mechanistic and causative insights into why and how communities vary over space and time, how communities adapt to change, and to develop new strategies for predictably modulating microbial community composition and function. Here, we focus on the targeted removal of a single species in a community. While adding an organism to an established model microbiome is relatively easy, the targeted removal of one species is more challenging. To address this challenge, we have developed a targeted bacteriophage lytic enzyme-based approach to selectively kill one organism in a model microbial community. Unlike conventional antibiotics, phage lytic enzymes have exquisite species specificity that target a single bacterial species or even a strain within a species. These lytic enzymes possess one of several cell wall peptidoglycan hydrolase activities with highly selective cell wall-binding specificities, which combine to confer activity and specificity toward a specific bacterial species. We have observed that Staphylococcus aureus can be selectively removed from co-cultures using the phage lytic enzyme lysostaphin (LST). Similarly, a second cell lytic enzyme, PlyPH, can be used to selectively remove Bacillus cereus. We have observed that the effectiveness of the selective killing depends on population density, lytic enzyme concentration and growth conditions. We will also present our work towards using Lst and PlyPH to selectively remove these organisms from a model human skin microbiome. S. aureus is a skin commensal in more than 30% of humans, while B. cereus is an opportunistic human skin pathogen. Such efforts are key to our long-term goal of being able to predictably modulate a target microbiome, based on causative or mechanistic insights, in order to alter microbiome function, or improve human health. The proposed project will also lay the groundwork for using targeted antimicrobial strategies for exploring microbiome dynamics and function in broad range of communities and environments.