**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** THE FARM-RAISED CATFISH INDUSTRY DOMINATES THE AQUACULTURE SECTOR IN THE UNITED STATES AND IS AN IMPORTANT ECONOMIC COMPONENT OF MISSISSIPPI, ALABAMA, AND ARKANSAS. EDWARDSIELLA ICTALURI IS A SIGNIFICANT PATHOGEN CAUSING ENTERIC SEPTICEMIA OF CATFISH (ESC). THERE ARE LIMITATIONS IN THE CURRENT THERAPEUTIC AND PREVENTATIVE STRATEGIES AGAINST ESC. THE PROBLEM IS EXACERBATED BY THE INCREASING EMERGENCE OF E. ICTALURI STRAINS RESISTANT TO THE APPROVED ANTIMICROBIALS. AS A RESULT, THERE IS AN URGENT, INDUSTRY-DEFINED NEED TO PROVIDE CATFISH PRODUCERS WITH A PRACTICAL, SAFE, AND EFFICACIOUS TREATMENT ALTERNATIVE. THIS PROPOSAL FOCUSES ON THE APPLICATION OF TRANS-CINNAMALDEHYDE (TC) AS A POSSIBLE SOLUTION TO CONTROL ESC INFECTION. TC IS A COMPOUND APPROVED AS A FOOD ADDITIVE BY THE U.S. FDA. OUR PRELIMINARY RESULTS AND PUBLISHED RESEARCH DEMONSTRATED THAT TC IS EFFECTIVE IN INHIBITING THE GROWTH OF E. ICTALURI, INCLUDING MDR STRAINS.THIS PROJECT INCLUDES CONDUCTING RESEARCH TO INVESTIGATE THE THERAPEUTIC AND PROPHYLACTIC POTENTIAL OF DIETARY-TC IN CATFISH AGAINST E. ICTALURI INFECTION, INCLUDING MULTIDRUG-RESISTANT (MDR) STRAINS. POND STUDIES WILL BE CONDUCTED TO TEST THE EFFICACY OF TC UNDER COMMERCIAL CONDITIONS. RESEARCH IN THIS PROJECT WILL ASSESS WHETHER TC IMPROVES PHAGOCYTIC AND BACTERICIDAL ACTIVITY OF MACROPHAGES AGAINST E. ICTALURI. WE WILL TEST ANOTHER PROTECTION MECHANISM OF DIETARY-TC AGAINST E. ICTALURI THROUGH IMPROVING INTESTINAL INNATE IMMUNE RESPONSE. THE STUDY ALSO INCLUDES AN ASSESSMENT OF THE POTENTIAL FOR E. ICTALURI TO DEVELOP RESISTANCE TO TC AND INVESTIGATE THE POSSIBLE MECHANISM OF TC ANTIBACTERIAL ACTION.THE ULTIMATE OUTCOME OF THIS PROJECT IS TO DEVELOP A MANAGEMENT STRATEGY TO CONTROL ESC INFECTION AND MINIMIZE AM USE IN CATFISH AQUACULTURE. WE EXPECT THAT APPLICATION OF TC AS A FEED ADDITIVE (POTENTIALLY PRODUCED BY COMMERCIAL FEED MILLS FOR SALE TO CATFISH PRODUCERS) WILL REDUCE THE MORTALITIES ASSOCIATED E. ICTALURI INFECTIONS AND WILL REDUCE COSTS AND THE CONSEQUENCES ASSOCIATED WITH SPREAD OF MDR STRAINS. THE APPROACH IMPLEMENTED IN THIS RESEARCH WILL ENSURE AQUACULTURE PRODUCERS HAVE ADEQUATE TREATMENT OPTIONS FOR MAXIMUM PRODUCTION EFFICIENCY, PROFITABILITY, AND SUSTAINABILITY.