**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** BACTERIAL INFECTION OF THE MAMMARY GLAND IN DAIRY CATTLE CAUSES MASTITIS, A DISEASE THAT ACCOUNTS FOR INCREASED COSTS TO NORTHAMERICAN DAIRY PRODUCERS THAT ARE ESTIMATED AT US$2 BILLION DOLLARS ANNUALLY. CONTRIBUTING TO THIS INCREASED COST ARE LOST MILKPRODUCTION, INCREASED COSTS OF TREATMENTS AND DEATH OF ANIMALS INFECTED ESCHERICHIA COLI BACTERIA. OVER 60% OF CATTLE SHOWINGSIGNS OF ILLNESS FROM MASTITIS ARE INFECTED WITH ESCHERICHIA COLI BACTERIA. CURRENT TREATMENTS ARE NOT RELIABLY EFFECTIVE, WITH OVER25% OF THE INFECTED COWS DYING OF SEVERE CLINICAL DISEASE. THE GOAL OF THIS PROJECT IS TO IDENTIFY ALTERNATIVE TREATMENTS THAT CANIMPROVE THE PROGRESSION AND SEVERITY OF DISEASE IN MAMMARY GLAND INFECTION WITH ESCHERICHIA COLI. IMPROVED TREATMENTS WILLIMPROVE ANIMAL WELFARE AND HELP WITH THE REDUCTION OF ANTIBIOTIC USE ON DAIRY FARMS, OF WHICH MASTITIS IS THE MAJOR REASON FORANTIBIOTIC USE.THE PROJECT WILL BE CONDUCTED USING A COMBINATION OF LABORATORY EXPERIMENTS AND ALSO LIVE ANIMALS THAT WILL BE EXPERIMENTALLYINFECTED WITH ESCHERICHIA COLI BACTERIA TO RECREATE THE NATURAL MASTITIS DISEASE CONDITION. THE ULTIMATE GOAL OF THE PROJECT IS TODEFINE THE SPECIFIC ROLE OF PATHWAY NOT PREVIOUSLY EXPLORED, KNOWN AS THE CYTOCHROME P450, IN DAIRY COWS WITH ESCHERICHIA COLIINFECTION. IDENTIFYING THE CYP450 WILL LEAD TO IMPROVED TREATMENTS, IMPROVE ANIMAL WELFARE, AND DECREASE THE USE OF ANTIBIOTICSIN ANIMAL AGRICULTURE. REDUCING THE USE OF ANTIBIOTICS MAY DELAY OR LIMIT THE DEVELOPMENT OF RESISTANCE TO MEDICALLY IMPORTANTANTIBIOTICS USED IN HUMAN HEALTH.