Targeting Lyme disease bacterium

Abstract

A major advance in the determination of the high-resolution crystal structures of protein variants from the Lyme-disease-causing bacterium could aid production of a more effective vaccine [EMBO J. (2001) 20, 971–978]. Lyme disease is caused by a spirochete, Borrelia burgdorferi, transmitted to humans by the bite of an infected deer tick. Probably the most common vector-borne disease in the USA, Lyme disease can lead to severe neurological complications if not appropriately treated. Currently, a first-generation vaccine exists, based on a Borrelia surface protein known as outer surface protein A (OspA). Because OspA is only expressed when spirochetes are residing in the midgut of unfed ticks, OspA-raised antibodies can only kill the bacterium if the tick ingests these antibodies while feeding on host blood. A joint research effort by investigators at the Brookheaven National Laboratory, Stony Brook University School of Medicine, the University of Rochester Medical Center and Rutgers University, has generated structures of variants of a second major Borrelia antigen, OspC. Although similarly expressed on the bacterial surface, unlike OspA, OspC is expressed during tick feeding, when bacteria are transferred into the host's bloodstream. This makes OspC an optimal candidate for a second-generation vaccine because antibodies against OspC would kill the invasive spirochetes within the host's body. Intriguingly, the new crystal structures indicate that OspC is predominantly helical, in contrast to OspA, which is mostly βsheet. AR