** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** MYCOPLASMA OVIPNEUMONIAE(M. OVI), WHICH CAN CAUSE RESPIRATORY INFECTIONS IN BOTH DOMESTIC AND WILD SHEEP. WHEN CO-INFECTED WITH ANOTHER SHEEP PATHOGEN CALLEDMANNHEIMIA HAEMOLYTICA,M. OVICAN LEAD TO SEVERE PNEUMONIA IN LAMBS, RESULTING IN PRODUCTION LOSSES.M. OVIINFECTIONS ARE OFTEN DRIVEN BY CARRIER ANIMALS THAT ARE PERSISTENTLY COLONIZED WITH THE BACTERIUM WITHOUT SHOWING SYMPTOMS. IN OUR RECENT EXPERIMENTS WITH SPECIFIC PATHOGEN-FREE DOMESTIC LAMBS, WE OBSERVED THATM. OVICAN ESTABLISH PERSISTENT COLONIZATION IN THE RESPIRATORY TRACT, WHICH IS RESISTANT TO BOTH THE LAMBS' IMMUNE SYSTEM AND ANTIBIOTIC TREATMENT.M. OVIESTABLISHES CHRONIC COLONIZATION IN THE AIRWAYS OF SHEEP BY INVESTIGATING THE INTERACTIONS BETWEEN THE HOST AND THE PATHOGEN. WE HYPOTHESIZE THAT BIOFILM FORMATION BYM. OVIPLAYS A CENTRAL ROLE IN IMMUNE EVASION AND ANTIBIOTIC RESISTANCE. WE HAVE THREE SPECIFIC AIMS: (1) TO MAP THE DISTRIBUTION OFM. OVIANDM. OVIBIOFILMS IN THE RESPIRATORY TRACT OF SHEEP, (2) TO DETERMINE HOW BIOFILM FORMATION AFFECTS THE SUSCEPTIBILITY OFM. OVITO ANTIBIOTIC TREATMENT, AND (3) TO IDENTIFY THE MECHANISMS BY WHICHM. OVIBIOFILMS IMPACT THE FUNCTION OF PHAGOCYTES, WHICH ARE IMMUNE CELLS THAT ENGULF AND DESTROY BACTERIA.M. OVIINFECTIONS IN SHEEP, INCLUDING THE POTENTIAL ELIMINATION OF THE BACTERIUM FROM FLOCKS.