** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** SALMONELLA IS A SIGNIFICANT PUBLIC HEALTH THREAT AND ECONOMIC CONCERN AS FOODBORNE ILLNESS CONTINUES TO BE AN OVERWHELMING CHALLENGE IN THE U.S. WHILE NUMEROUS INTERVENTION STRATEGIES ARE USED IN POULTRY PROCESSING TO REDUCESALMONELLAPOPULATIONS WITH SOME SUCCESS, P LIVE BIRD PRODUCTION REMAINS A CRITICAL STEPFORSALMONELLACONTROL. USING8 TO12 HOUR FEED WITHDRAWAL (FW) BEFORE THEBROILERS ENTERTHE PROCESSING PLANTTO REDUCE FECAL CONTAMINATION APPEARS TO BE A MAJOR FACTOR TO INCREASES IN SALMONELLA. OUR RESEARCH PROPOSAL REPRESENTS AN NEWWAY FOR SALMONELLA CONTROL WITH ATARGETED BIOENGINEERING DESIGNOF A MULTIPLE PHAGE POPULATION WITH AN OPTIMIZEDSALMONELLA-KILLINGIMPACT THAT CAN BE APPLIED DURING FW TO REDUCE MOST IF NOT ALLSALMONELLA SEROVARS AND STRAINS.OURGENERAL HYPOTHESISIS THAT BIOENGINEERING PHAGES WITH DIFFERENT SALMONELLAATTACHMENT SITES ALLOW FOR THEIR MAXIMUM AND CONTINUOUS EXPOSURE TO TARGETSALMONELLA PREVENTINGHORIZONTALSALMONELLATRANSMISSIONAMONG BIRDS DURING FW REDUCING SALMONELLA PREVALENCE AT THE PROCESSING PLANT.OUR SPECIFIC OBJECTIVES:OBJECTIVE 1- BIOENGINEER BACTERIOPHAGES FOR OPTIMAL EFFICACY AGAINSTSALMONELLASEROVARS DURING FW.OBJECTIVE 2 -SCREEN THE RESULTING BIOENGINEERED PHAGE CANDIDATES FROMOBJECTIVE 1AGAINST MULTIPLESALMONELLASEROVARS USING IN VITRO CROP AND CECAL INCUBATIONS.OBJECTIVE 3- DETERMINE THE EFFICACY OFSALMONELLAPHAGE COCKTAIL IDENTIFIED IN OBJECTIVE 2 SUPPLEMENTED IN THE DRINKING WATER OF COMMERCIAL BROILERS ON REDUCINGSALMONELLATRANSMISSION DURING FW AND SALMONELLA LOAD AT THE PROCESSING PLANT.THE RESULTS FROM THIS RESEARCH OCCUR AT A MOST OPPORTUNE TIME FOR THE MEAT AND POULTRY INDUSTRY AS THE INDUSTRY IS NOW CONSIDERING BACTERIOPHAGES AS A POTENTIAL APPROACH FOR LIMITING PATHOGENS. MOREOVER, THE INDUSTRY IS DESPERATE FOR VIABLE OPTIONS. OUR COLLABORATIVE APPROACH CONCEPTUALLY REPRESENTS A HIGHLY TARGETED STRATEGY BY BIOENGINEERING MORE EFFICACIOUS PHAGE FOR THE POULTRY GIT AND TAILORED FOR APPLICATION DURING FW BEFORE POULTRY PROCESSING. IN ADDITION, OUR BIOENGINEERED PHAGE APPROACH REPRESENTS A BROAD-SPECTRUM INTERVENTION TO MOST SEROVARS BOTH CURRENTLY PREVALENT ONES AS WELL AS EMERGING SEROVARS. POULTRY IS ONLY THE BEGINNING. SALMONELLA IS ALSO PREVALENT IN SWINE, CATTLE, AND NONMEAT FOODS SUCH AS VEGETABLES. WITH TRADITIONAL INTERVENTIONS, SALMONELLA CAN BE ESPECIALLY DIFFICULT TO TACKLE IN SWINE AND CATTLE ONCE THEY INVADE DEEP TISSUES WHERE PHAGE APPLICATION COULD BE PRACTICAL. FINALLY, FROM MORE OF A LONG-TERM STANDPOINT, THIS APPROACH OPENS THE FLOODGATES TO TACKLE OTHER PATHOGENS WHICH ARE ALSO HIGHLY PROBLEMATIC FOR THE POULTRY INDUSTRY, SUCH AS CAMPYLOBACTER, WHICH RESIDES IN THE CHICKEN GUT AS PART OF THE MICROBIOME AND IS NEARLY IMPOSSIBLE TO TARGET WITH ANTIMICROBIALS.