Role of Borrelia burgdorferi Envelope in the Pathogenesis of Lyme Disease

Borrelia burgdorferi (Bb), the causative agent of Lyme disease, has a compact genome with limited metabolic capabilities and is therefore a highly host-adapted pathogen with capabilities to withstand multiple antimicrobial factors prevalent during the vector and mammalian phases of infection. The cell envelope of Bb support the bacterium's survival under highly divergent environmental signals and host defense mechanism prevalent in different hosts. Bb cell envelope comprises of an outer membrane with a constellation of lipoproteins, a Peptidoglycan (PG) cell wall, periplasmic space and an inner membrane. In addition to providing structural and morphological integrity of Bb, PG serves as a persistent antigen in Lyme disease patients with L-Ornithine as the third amino acid that cross-links its glycan polymers. I identified and characterized the contributions a protein designated as Borrelia peptidoglycan interacting Protein (BpiP) with a conserved domain for interaction with PG in the patho-physiology of Bb. BpiP was localized to the periplasmic cylinder and crosslinking studies revealed its interactions with PG. A mutant lacking bpiP was significantly attenuated for infection following challenge of C3H/HeN mice compared to control strains at day 28 post-infection. Loss of bpiP resulted in reduced transmission of spirochetes from I. scapularis nymphs to naive mice. Further analysis of bpiP mutant exhibited increased sensitivity to various environmental stressors, soluble and cellular components of innate and adaptive immunity in mouse models of infection. These studies demonstrate the importance of accessory protein/s involved in sustaining integrity of PG during the tick and mammalian phases of Bb infection.