NON-TYPHOIDAL SALMONELLA (NTS) ARE THE LEADING CAUSE OF BACTERIAL FOOD-BORNE GASTROENTERITIS IN HUMANS CAUSING HUNDREDS OF MILLIONS CASES IN HUMANS AND LIVESTOCK. THERE IS NO TREATMENT FOR UNCOMPLICATED GASTROINTESTINAL NTS INFECTIONS BECAUSE CURRENTLY AVAILABLE ANTIBIOTICS (A) DO NOT TO IMPROVE THE CLINICAL OUTCOME, (B) PROLONG THE DURATION OF FECAL SHEDDING, AND (C) CONTRIBUTE TO DEVELOPING ANTIBIOTIC RESISTANCE. HUMANS CAN ACQUIRE SALMONELLOSIS BY CONSUMING CONTAMINATED POULTRY OR POULTRY PRODUCTS. THE GOAL OF THIS PROPOSAL IS TO DEVELOP POTENTIAL PRODUCTS TO INTERFERE WITH SALMONELLA COLONIZATION OF THE CHICK INTESTINE, AND THUS REDUCE TRANSMISSION OF SALMONELLA TO HUMANS. WE HYPOTHESIZE THAT A PRODUCT OF THE NORMAL BACTERIAL MICROBIOTA OF THE CHICK (FORMATE), IS THE KEY MICROBIAL PRODUCT THAT ALLOWS SALMONELLA TO GAIN A FOOTHOLD IN THE CHICK INTESTINE AND ESTABLISH SUBCLINICAL COLONIZATION. TO INTERROGATE THIS HYPOTHESIS, WE WILL: (1) IDENTIFY THE SALMONELLA GENES NEEDED FOR FORMATE USE IN THE CHICK, (2) DEFINE HOW MUCH FORMATE IS PRESENT DURING MATURATION OF THE CHICK AND CORRELATE THIS WITH CHANGES IN THE COMPOSITION OF THE NORMAL MICROBIOTA PRESENT, AND (3) TEST COMMENSAL E. COLI "NISSLE" STRAINS THAT CAN NOT PRODUCE FORMATE FOR THEIR ABILITY TO LOWER SALMONELLA COLONIZATION IN CHICKS. SUCCESSFUL COMPLETION OF THIS PROJECT WILL LEAD TO A DETAILED UNDERSTANDING OF THE FACTORS THAT PROMOTE SUBCLINICAL COLONIZATION OF CHICKS WITH SALMONELLA, AND LEAD TO THE DEVELOPMENT OF A RATIONALLY DESIGNED PROBIOTIC TO REDUCE SALMONELLA COLONIZATION IN CHICKS.