APEC IS A LEADING CAUSE OF MORBIDITY AND MORTALITY IN POULTRY AND RESULTS IN MULTI-MILLION DOLLAR ANNUAL LOSSES FOR ALL FACETS OF THE POULTRY INDUSTRY. CURRENTLY, APEC INFECTIONS IN POULTRY ARE CONTROLLED BY ANTIBIOTICS MEDICATION AND VACCINATION. HOWEVER, APEC ISOLATES ARE BECOMING MORE RESISTANT TO ANTIBIOTICS AND THE CURRENTLY AVAILABLE VACCINES ARE ONLY EFFECTIVE AGAINST HOMOLOGOUS SEROTYPE, O78. THERE IS A CRITICAL NEED FOR DEVELOPING NOVEL ANTI-APEC THERAPEUTICS TO IMPROVE THE CONTROL OF THIS KEY ENDEMIC AVIAN DISEASE. THROUGH OUR RECENT INNOVATIVE SMALL MOLECULES BASED STUDIES, WE HAVE IDENTIFIED PROMISING ANTI-APEC LEADS [GROWTH INHIBITORS (GI-7, GI-10) AND QUORUM SENSING INHIBITORS (QSI-5 AND QSI-10)]. THESE LEAD MOLECULES IN SMALL PILOT STUDIES REDUCED THE APEC INDUCED MORTALITY OF CHICKENS, REDUCED THE APEC LOAD IN CHICKEN INTERNAL ORGANS AND LESSEN THE SEVERITY OF APEC LESIONS. IN ADDITION, THESE LEADS ARE EFFECTIVE AGAINST DIVERSE APEC SEROTYPES, ANTIBIOTIC-RESISTANT APECS AND AGAINST BIOFILM PROTECTED APEC. HERE, WE WILL EVALUATE THE THERAPEUTIC POTENTIAL OF THESE LEAD MOLECULES UNDER EXPERIMENTAL AND NATURAL SETUP AS WELL AS ELUCIDATE THEIR MECHANISMS OF ACTION. THE DEMONSTRATION OF THE EFFICACY, SAFETY AND APPLICABILITY OF THESE LEAD MOLECULES IN CHICKENS IS VITAL TO ADVANCE THEM AS NOVEL ANTI-APEC THERAPEUTICS. OUR STUDY WILL HELP TO PROMOTE SUSTAINABLE POULTRY PRODUCTION WORLDWIDE TOGETHER WITH IMPROVED FOOD SECURITY AND FOOD SAFETY.