Aims: The scientific goal of this project is to evaluate PGHs as novel antimicrobials against S. iniae in tilapia and HSB. PGH use can be translated to other fish pathogen species as well as for animal and human diseases. To achieve our goal, we will address the following three aims:Aim 1. Create PGHs fused to PTDs and screen for the killing of planktonic (30 strains) and intracellular forms of S. iniae in cultured immortalized fish cell lines. (Grace Ramena,UAPB)Aim 2. Demonstrate the efficacy of the optimal constructs (high activity and high species specificity PGH's and PGH-PTDs) to prophylactically and/or therapeutically treat S.iniae in established Nile tilapia (Craig Shoemaker, ARS, Auburn, AL) and hybrid striped bass (HSB) (David Crosby, VSU) IP infection models.Aim 3. Evaluate in vivo efficacy of Tg yeast expressing PGH via fish feed using an oral S. iniae infection model. (C. Skory, ARS, Peoria, IL, C. Shoemaker, and D. Crosby).