There is a critical need for novel tools to manage disease outbreaks at aquaculture facilities. Bacteria belonging to the genusPhaeobacterhave emerged as highly promising targets for development asprobiotic additives to prevent infectious diseases in marine larviculture through microbial-microbial interactions.We have demonstrated the safety and effectiveness ofPhaeobacterinhibens(S4) inprotecting bivalveshellfish larvae againstbacterial pathogens, and developed a commerciallyavailableformulationproviding consistent protection of larvae treated in the hatchery against challenge with the marine pathogenVibrio coralliilyticusRE22.We have also elucidated several complex, critical molecular mechanisms used byPhaeobacterto outcompete pathogens and improve host survival; however,knowledge gaps remain in fullyunderstanding these interspecies interactions.Additionally, we lack a complete understanding of the virulence mechanisms employed by well-established aquaculture pathogens. This lack of knowledge prevents the rational development of probiotics as disease management tools for aquaculture and limits our ability to identify disease causing strains and understand the mechanisms by which they kill hosts and outcompete commensal microorganisms.Thelong-term goalof our investigation is to develop tools for bacterial disease management in aquaculture (and alternatives to antibiotic treatment). In the current proposal, we seek to more broadly explore applicationsfor usingS4treatments tolimit disease outbreaks in aquaculture systemsby exploiting knowledge of probiont-pathogen interactions.We will alsoclose existing knowledge gaps in themolecular mechanisms of pathogenesis used by RE22 during infection.Thegoals for this proposalareto (1)elucidate previously unexplored virulence mechanisms inRE22pathogenesis,and (2) explore how probiontP. inhibens S4 modulates virulence pathways in other prominent marine pathogens.