CAMPYLOBACTER IS A MAJOR FOODBORNE PATHOGEN AND A LEADING BACTERIAL CAUSE OF GASTROENTERITIS IN THE UNITED STATES AND OTHER COUNTRIES. CLINICAL TREATMENT OF CAMPYLOBACTERIOSIS REQUIRES THE USE OF FLUOROQUINOLONE (FQ) OR MACROLIDE ANTIBIOTICS, BUT ANTIBIOTIC-RESISTANT CAMPYLOBACTER IS INCREASINGLY PREVALENT, COMPROMISING THE EFFICACY OF CLINICAL TREATMENT. BECAUSE OF ITS SIGNIFICANCE TO PUBLIC HEALTH, CDC HAS RECENTLY IDENTIFIED DRUG-RESISTANT CAMPYLOBACTER AS A SERIOUS ANTIBIOTIC RESISTANCE THREAT IN THE U.S. CAMPYLOBACTER IS HIGHLY PREVALENT IN FOOD PRODUCING ANIMALS, AND RUMINANTS ARE IMPORTANT RESERVOIRS FOR THIS PATHOGENIC ORGANISM. RUMINANT CAMPYLOBACTER CAN BE TRANSMITTED TO HUMANS VIA CONTAMINATED MILK AND WATER, OR DIRECT CONTACT. ADDITIONALLY, RUMINANTS ARE AN IMPORTANT PART OF CAMPYLOBACTER ECOLOGY AND MAY SERVE AS A SOURCE OF CAMPYLOBACTER TRANSMISSION TO OTHER FARM ANIMALS, SUCH AS POULTRY. PREVIOUSLY, MOST EFFORTS ON ANTIBIOTIC-RESISTANT CAMPYLOBACTER WERE DEVOTED TO POULTRY, WHICH LED TO WITHDRAWAL OF FQ ANTIMICROBIALS FROM POULTRY PRODUCTION IN THE U.S. IN 2005. HOWEVER, NATIONAL SURVEILLANCE DATA INDICATE THAT FQ-RESISTANT CAMPYLOBACTER CONTINUES TO PERSIST AND EVEN SHOWS A RISING TREND AFTER FQ WITHDRAWAL IN POULTRY, SUGGESTING THAT ALTERNATIVE SOURCE(S) OF FQ-RESISTANT CAMPYLOBACTER MAY EXIST. OUR RECENT STUDY ON CAMPYLOBACTER ISOLATES FROM FEEDLOT CATTLE HERDS IN VARIOUS GEOGRAPHIC REGIONS REVEALED A SHARP INCREASE IN PROPORTIONS OF FQ-RESISTANT CAMPYLOBACTER IN CATTLE IN THE U.S. DURING THE PAST DECADE, WHICH COINCIDED WITH THE APPROVED USE OF FLUOROQUINOLONE ANTIMICROBIALS FOR CONTROL AND TREATMENT OF RESPIRATORY DISEASE IN CATTLE. TO REDUCE THE PREVALENCE OF FQ-RESISTANT CAMPYLOBACTER IN THE FOOD CHAIN, WE HAVE DEVELOPED A 3-YEAR INTEGRATED PROJECT TO IDENTIFY CRITICAL CONTROL POINTS FOR DEVELOPING MITIGATION STRATEGIES, DISSEMINATE SCIENCE-BASED KNOWLEDGE TO CATTLE PRODUCERS AND VETERINARIANS, AND TRAIN VETERINARY MEDICINE STUDENTS WITH HANDS-ON EXPERIENCE IN ANTIBIOTIC RESISTANCE RESEARCH. SPECIFICALLY, WE WILL 1) IDENTIFY CRITICAL CONTROL POINTS FOR MITIGATING THE DEVELOPMENT OF FQ-RESISTANT CAMPYLOBACTER IN CATTLE BY EVALUATING THE SELECTIVE PRESSURE IMPOSED BY DIFFERENT FQ TREATMENT REGIMENS, 2) UNDERSTAND THE EFFECT OF FQ TREATMENT ON GUT MICROBIOTA AND FQ RESISTANCE BY USING A METAGENOMICS APPROACH, AND 3) DEVELOP OUTREACH AND TRAINING PROGRAMS TO REDUCE FQ-RESISTANT CAMPYLOBACTER. THE PROPOSED WORK INVOLVES SIGNIFICANT PARTICIPATION BY STAKEHOLDERS AND DIRECTLY ADDRESSES MULTIPLE PRIORITY AREAS OF PROGRAM A4171 (EFFECTIVE MITIGATION STRATEGIES FOR ANTIMICROBIAL RESISTANCE). THE ACTIVITIES WILL YIELD IMPORTANT OUTCOMES THAT WILL REDUCE THE TRANSMISSION OF ANTIBIOTIC RESISTANT FOODBORNE PATHOGENS, IMPROVE FOOD SAFETY, AND ENHANCE THE SUSTAINABILITY OF THE U.S. CATTLE INDUSTRY.