**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** THIS STUDY IS FOCUSED ON MYCOPLASMA OVIPNEUMONIAE, A BACTERIUM THAT INFECTS THE RESPIRATORY TRACT OF SHEEP. M. OVIPNEUMONIAE CAN LEAD TO ASYMPTOMATIC COLONIZATION IN ADULT DOMESTIC SHEEP, MILD RESPIRATORY DISEASE AND OCCASIONAL PNEUMONIA IN DOMESTIC LAMBS, AND SEVERE OUTBREAKS OF DEADLY PNEUMONIA IN BIGHORN LAMBS AND OTHER WILD RUMINANTS. WHY THIS OPPORTUNISTIC PATHOGEN CAUSES SUCH A WIDE RANGE OF DISEASE OUTCOMES IS NOT FULLY UNDERSTOOD. OUR OVERARCHING GOAL IS TO ELUCIDATE THE HOST- AND PATHOGEN-SPECIFIC MECHANISMS THAT ENABLE CHRONIC ASYMPTOMATIC M. OVIPNEUMONIAE INFECTIONS AND TO DEVELOP STRATEGIES TO ELIMINATE THESE INFECTIONS IN ORDER TO PREVENT CLINICAL DISEASE. SPECIFICALLY, WE WILL (1) DEFINE THE CONDITIONS THAT ARE ASSOCIATED WITH PERSISTENT, ASYMPTOMATIC M. OVIPNEUMONIAE COLONIZATION IN DOMESTIC SHEEP; (2) IDENTIFY BACTERIAL IMMUNE EVASION STRATEGIES THAT PROMOTE M. OVIPNEUMONIAE PERSISTENCE IN THE RESPIRATORY TRACT OF DOMESTIC SHEEP; (3) EXPLORE TREATMENT STRATEGIES TO ELIMINATE PERSISTENT M. OVIPNEUMONIAE INFECTION. PREVENTING CLINICAL M. OVIPNEUMONIAE INFECTIONS IN LAMBS BY ELIMINATING ADULT CARRIER ANIMALS WILL HAVE SIGNIFICANT EFFECTS ON SHEEP HEALTH AND PRODUCTION AND MAY ALSO PROTECT BIGHORN SHEEP FROM DEVASTATING PNEUMONIA OUTBREAKS.