Edwardsiella ictaluri is the causative agent of enteric septicemia of catfish (ESC) and one of the most significant pathogens of US catfish aquaculture. The current therapeutic strategies to prevent ESC have their limitations, and catfish operations continue to suffer significant losses due to ESC. Therefore, it is necessary to find safe and efficacious alternative therapies to control ESC outbreaks, thereby reducing the use of antimicrobials (AMs) in catfish aquaculture and minimizing selective pressure that results in antimicrobial resistant (AMR) strains.The long-term goal of our working group is to 1) identify potential intervention strategies to reduce catfish mortality associated with bacterial infections and 2) extend the effectual lifespan of currently approved AMs. Our hypothesis is that direct administration of trans-cinnamaldehyde (TC) in catfish feed is an effective treatment for ESC, and dietary-TC enhances survival of catfish during E. ictaluri infection through the antibacterial activity of TC and immunomodulatory effects in catfish. Our specific objectives for this proposal are:Determine efficacy of dietary-TC to prevent and treat Edwardsiella ictaluri infection in catfish. In this aim, we will optimize TC application regime to achieve maximum protection from E. ictaluri infection, including MDR strains. Also, we will test the efficacy of dietary-TC to control ESC in experimental research ponds under simulated industry conditions. Explore the mechanisms by which TC-supplemented diet provides protection of catfish against E. ictaluri. In this aim, we will assess the effects of dietary-TC on innate immune response of catfish as a mechanism by which dietary-TC improves catfish survival during ESC.Evaluate the ability of E. ictaluri to develop resistance to TC and determine the major mechanism(s) of TC antibacterial action. In this aim, we will investigate the possibility of the emergence of resistance in E. ictaluri after repeat exposure to TC. We will also determine mechanisms of TC antibacterial action against E. ictaluri.