Infectious diseases are the chief cause of production loss in aquaculture and have severely limited the growth and sustainability of this industry. Gram-positive streptococci are costly pathogens that cause diseases in the aquaculture industry. Specifically, Streptococcus iniae is an emerging pathogen of wild and cultured fish, with ~30 species of fish susceptible to this pathogen. The economic impact of streptococcosis on the global aquaculture industry is hundreds of millions of dollars annually. While antibiotics are effective against many bacterial infections of fish, there are fears that their use in aquaculture may cause severe environmental and human health problems. In addition, the use of antibiotics in aquaculture has led to resistance in targeted pathogens, which could reduce their effectiveness. Although antibiotic treatment is effective, multi-drug resistant strains may lead to a potential for farm-to-clinic antibiotic-resistance transfer. These potential complications have led to an intensive effort to develop safer alternatives to traditional antibiotics. These novels (non-antibiotic) antimicrobials should be refractory to resistance development. Phage endolysins are cell wall degrading peptidoglycan hydrolases (PGHs), enzyme antimicrobials that digest peptidoglycan, the major structural component of the bacterial cell wall. Using bioinformatic tools, we identified ten PGHs that can potentially prevent and or eradicate systemic and topical S. iniae from fish. We used the pET21a (+) vector to express PGH-6x His tag in BL21 (DE3) E. coli, purified the proteins, and tested against S.iniae strains. Our preliminary data suggests new potential alternatives to antibiotics to treat streptococcosis.