Grant: Project Grant

Lyme disease is an emerging infectious disease caused by a spiral-shaped bacterium or spirochete (Borrelia burgdorferi) that is transmitted through the bite of an infected tick. Incidence of the disease is increasing, triggered in part by global warming. The disease can result in a wide variety of symptoms, often making diagnosis difficult. The focus of this project is to investigate two important strategies used by B. burgdorferi to mount a successful infection. 1) Antigenic variation. This is a process by which the pathogen continually changes the sequence of the major component of the outer coat resulting in a continual wardrobe change for the pathogen. This keeps it one step ahead of the immune system, resulting in persistent infection. Antigenic variation is driven occurs by continual DNA rearrangements in the gene for the major surface protein, VlsE. We will study this process in detail including the DNA regions and protein molecules involved in the rearrangement process. 2) Vascular transmigration. The reason why B. burgdorferi can cause such a large number of different symptoms is because the organism disseminates through the circulatory system and can exit the vasculature in virtually any part of the body. The result is varying symptoms depending upon where B. burgdorferi exits the bloodstream. Vascular transmigration is mediated by interactions between B. burgdorferi and endothelial cells lining small blood vessels. We will investigate these interactions and the changes they cause as well as the proteins and signaling pathways involved and the molecular changes occurring to the endothelial layer that unlock the door for spirochete escape. Significance: Details uncovered on these important processes may be useful for future development of clinical interventions. Blocking vascular transmigration would stop dissemination of the spirochetes from the site of a tick bite and eliminating antigenic variation would eradicate persistent infection.