Lyme disease is a bacterial infection transmitted by the bite of an infected tick carrying the bacterium Borrelia burgdorferi . More than 47 million people are diagnosed in the United States annually, as its cases have been rising throughout the world. Lyme disease is a major public health concern and faces challenges in developing a vaccine due to limited understanding of the bacterium. B. burgdorferi is identified as the major etiologic pathogen of this illness and is transferred to the secondary host's bloodstream by a tick bite and then disseminates to various tissues, causing Lyme disease symptoms such as Lyme neuroborreliosis, Lyme carditis, or Lyme arthritis. Outer membrane proteins decorate the outer surface of the pathogen. Specifically, the outer surface protein A (OspA) is the major outer membrane protein of the B. burgdorferi . OspA plays a critical role in the bacterium's life cycle and pathogenesis. It mediates the colonization of bacteria in the tick’s midgut by binding to the tick’s specific receptor, TROSPA. This binding is essential for the bacteria’s survival and subsequent transmission. While the monomeric structure has been elucidated, a complete understanding of its oligomeric state and the specific details of its lipidation site remains unrevealed. The ultimate goal is to determine the first high-resolution structure of oligomeric ospA using cryogenic electron microscopy and demonstrate how this structure contributes to its interaction with its receptor. A comprehensive structural analysis in its native oligomeric state, including its lipid modification, is vital for a full understanding of its role in Lyme disease pathogenesis and for the development of effective therapeutic intervention.
Kim et al. (2026) studied this question.