UNDERSTANDING THE ECOLOGY OF ANTIMICROBIAL RESISTANCE (AMR) AND CONTROL OF HEMOPARASITIC DISEASES ARE NATIONAL PRIORITIES FOR THE UNITED STATES DEPARTMENT OF AGRICULTURE (USDA) AND ARE VITAL TO PROTECTING OUR FOOD SECURITY AND THE CONTINUED SUSTAINABLE DEVELOPMENT OF OUR LIVESTOCK INDUSTRIES. JUDICIOUS USE OF ANTIMICROBIALS ARE ESSENTIAL TO MAINTAIN SUSCEPTIBLE BACTERIAL POPULATIONS AND PROMOTE ANTIMICROBIAL LONGEVITY, WHILE MINIMIZING DEVELOPMENT OF RESISTANT MICROBIAL POPULATIONS. HOWEVER, SEVERAL CURRENTLY FOOD AND DRUG ADMINISTRATION (FDA)-APPROVED MEDICATED LIVESTOCK FEED THERAPIES UTILIZE MEDICALLY IMPORTANT ANTIMICROBIALS WITH NO ON-LABEL DEFINED DURATION OF USE, SUCH AS THE USE OF CHLORTETRACYCLINE (CTC)-MEDICATED FEEDS FOR THE TREATMENT OF BOVINE ANAPLASMOSIS (ANAPLASMOSIS) IN CATTLE. UNINTENDED CONSEQUENCES OF PROLONGED ANTIMICROBIAL EXPOSURE, ESPECIALLY AT SUB-THERAPEUTIC DOSES, INCLUDE SELECTION OF AMR IN BOTH THE TARGET PATHOGEN AND OFF-TARGET ZOONOTIC COMMENSALS. BASED ON THE PREMISE THAT INCREASING EXPOSURE OF BACTERIAL POPULATIONS TO ANTIMICROBIAL DRUGS INCREASES OF THE RISK OF POPULATIONS GENERATING RESISTANCE TO THOSE DRUGS, THE FDA, THROUGH THE FEDERAL REGISTER, HAS SOUGHT INFORMATION TO HELP ESTABLISH APPROPRIATE DOSE AND DURATION OF USE POLICIES WHEREBY CLINICAL THERAPEUTIC EFFECT IS MAXIMIZED AND RISK OF RESISTANCE DEVELOPMENT IS MINIMIZED. THE LONG-TERM GOAL OF THIS PROGRAM OF WORK IS TO PROMOTE SUSTAINABLE LIVESTOCK PRODUCTION BY REDUCING PROTRACTED ANTIMICROBIAL EXPOSURE TO CONTROL INFECTION OF THE HEMOPARASITIC RICKETTSIAL PATHOGEN, ANAPLASMA MARGINALE (AM), THE ETIOLOGIC AGENT OF ANAPLASMOSIS IN CATTLE. THE GUIDING HYPOTHESIS OF THIS PROPOSAL IS THAT TARGETING TREATMENT WITH TETRACYCLINE (TET) ANTIMICROBIALS TO COINCIDE WITH STRATEGIC PERIODS IN THE AM TRANSMISSION CYCLE WILL EFFECTIVELY CONTROL CLINICAL ANAPLASMOSIS IN CATTLE WHILE ALSO MINIMIZING DEVELOPMENT OF AMR IN AM AND OFF-TARGET (BOVINE ZOONOTIC COMMENSALS) BACTERIAL SPECIES. INFORMED BY SCIENTIFIC DATA AND THROUGH ACTIVE, INTEGRATED COOPERATION BETWEEN SCIENTISTS, CLINICIANS, EXTENSION, AND PRODUCERS, THIS PROPOSAL WILL ENABLE LIVESTOCK PRODUCERS TO MAKE MORE EFFICIENT USE OF ANTIMICROBIALS BY ALIGNING ANTIMICROBIAL USAGE WITH THE NATURAL BIOLOGICAL CYCLE OF AM TO OPTIMIZE DISEASE CONTROL. THE PRIMARY OBJECTIVES OF THIS PROPOSAL ARE TO: I) EXAMINE THE IN VIVO EFFICACY OF TET ANTIMICROBIALS TO CONTROL ANAPLASMOSIS IN EXPERIMENTAL AND FIELD CHALLENGES, II) EVALUATE THE ANTIMICROBIAL SUSCEPTIBILITY PROFILE OF TARGET (AM) AND OFF-TARGET (BOVINE ZOONOTIC COMMENSALS) MICROBIAL SPECIES IN TREATED CATTLE; III) DETERMINE THE CONTRIBUTION OF AM TICK VECTOR SPECIES TO THE ECOLOGICAL PERSISTENCE OF AMR IN AM POPULATIONS; AND IV) DEVELOP AN EXTENSION PLATFORM TO PROVIDE RESOURCES TO STAKEHOLDERS TRYING TO MITIGATE ANAPLASMOSIS AND SUPPORT ANTIMICROBIAL STEWARDSHIP.