** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** CLOSTRIDIOIDES DIFFICILE IS AN IMPORTANT PATHOGEN OF FOOD ANIMALS (ESPECIALLY PIGLETS), AND CAUSES THE DIARRHEAL DISEASE C. DIFFICILEINFECTION (CDI). IN SWINE OPERATIONS, C. DIFFICILE IS ROUTINELY RECOVERED FROM PIGLETS AND SOWS. COLONIZED PIGLETS CAN SHED C. DIFFICILE OVER PROLONGED PERIODS OF TIME, CAUSING ADDITIONAL CYCLES OF INFECTION. A SPECIFIC PHYLOGENETIC LINEAGE OF C. DIFFICILE (RT078) IS COMMONLY FOUND IN AGRICULTURALLY-IMPORTANT ANIMALS. RT078 STRAINS HAVE ALSO BEEN RECOVERED FROM HUMAN PATIENTS, LEADING TO THE CONTENTION THAT FARMS/FOOD MAY BE RESERVOIRS OF THE PATHOGEN. RT078- MEDIATED CDI MAY THUS BE CONSIDERED AS A QUINTESSENTIAL ONE HEALTH PROBLEM. INDEED, OUR 10-YEAR, PROSPECTIVE CDI SURVEILLANCE OF ARIZONA HOSPITALS AND SWINE OPERATIONS ALIGNS CLOSELY WITH THAT OF THE CDC'S EMERGING INFECTIONS PROGRAM AND REVEALS THAT C. DIFFICILE RT078 IS PREVALENT IN BOTH AGRICULTURAL, AND HUMAN HEALTHCARE, SETTINGS. DESPITE ITS IMPORTANCE TO BOTH ANIMAL AND HUMAN HEALTH, THE MECHANISMS UNDERLYING RT078 VIRULENCE AND TRANSMISSION IS POORLY UNDERSTOOD. OUR RECENTLY PUBLISHED PRELIMINARY DATA INDICATE THAT RT078 STRAINS HAVE SIGNIFICANTLY DIFFERENT BIOLOGY COMPARED TO OTHER, HUMAN-PREVALENT, C. DIFFICILE LINEAGES.