Grant: Project Grant

Lyme disease is an emerging infectious disease caused by a spiral-shaped bacterium (Borrelia burgdorferi) that is transmitted to humans 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, mimicking other medical conditions, 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 that is recognized by antibodies. The outcome is a continual wardrobe change for the pathogen that keeps it one step ahead of host recognition resulting in persistent infection. Antigenic variation occurs by continual DNA rearrangements in the gene for the major surface protein, VlsE. We will study this process in detail using next generation sequencing. We will also study the DNA regions involved in the rearrangement process and the protein molecules that promote the DNA rearrangements. 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. The process of 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 in blood vessels that allow B. burgdorferi to exit. We will also study the proteins and signaling pathways involved and the molecular changes occurring to the endothelial layer that unlock the door for escape. Details uncovered on these important processes may be useful for future development of clinical interventions.