Unique features of B. burgdorferi peptidoglycan drive persistence in discrete tissues and cause responses that mimic chronic illness 9279

Abstract Description Lyme arthritis (LA), a debilitating symptom of Lyme disease (LD), affects ∼50,000 people each year in the U.S. Some patients also experience chronic fatigue, even after treatment. How the causative agent Borrelia burgdorferi (Bb), which lacks classical virulence factors, causes Lyme disease symptoms is not known. The chemically unique peptidoglycan (PG) of Bb persists in the synovial fluid of LA patients after therapy and is thought to act as a persistent antigen. To study 1) the biodistribution of Bb PG in mice, 2) its clearance rate, and 3) its overall impact on the host in vivo we developed a novel method to track purified PG in real time. We found polymeric Bb PG persists in the liver for weeks, which was much longer than PG with typical chemistry. Hepatocytes and Kupffer cells were also found to preferentially engulf and retain Bb PG. While the presence of Bb PG didn’t affect the pathology of the liver, it did alter the secretion and overall protein profile of the organ. On a transcriptomic level, Bb PG impacts energy related pathways. Our multiomic studies uncovered similarities in metabolic dysregulation seen in patients suffering from other chronic illnesses induced post infection. Studying Bb PG provides insight into how a specific bacterial component can continue to persist and elicit an immune response even after apparent bacterial clearance. Funding Sources Supported by NIAID/R21AI159800, NIAID/R01AI173256, NIAID/R01AI178711, DOD/TB220039 Steven and Alexandra CohenFoundation Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)