Structure of OspA surface protein from Lyme disease bacterium.

Lyme disease, a bacterial infection transmitted to humans through a tick bite, causes rashes, fever, arthritis, and nerve damage and is an increasing concern in the northeastern United States. Although treatable with antibiotics, Lyme disease can be difficult to diagnose, and untreated infections can progress to severe complications. Accordingly, scientists have sought to design a safe, effective vaccine. The original Lyme disease vaccine often failed, for reasons that were unclear until Cathy Lawson and John Dunn at Brookhaven National Laboratory explained why. Using intense X-rays at the National Synchrotron Light Source, they identified variations in the structure of a key surface protein, OspA, from the bacterium that causes Lyme disease. The OspA structure contains several regions that vary among different strains of the bacterium and other regions that are invariant. The original vaccine was developed against a variant region from only one strain, so it did not protect against other strains. Continuing Brookhaven research on other Lyme disease proteins could lead to further improvements in vaccines.

Scientific Impact: The structural model of OspA, showing the exact locations where different strains of the bacterium vary, helped researchers quickly solve an urgent problem. This work also demonstrated the value of the latest synchrotron technologies.

Social Impact: The second-generation vaccines—protecting against many strains of the bacterium—have been commercialized and are much more effective than earlier versions in inducing general immunity to, and preventing, Lyme disease in people. Brookhaven research on other Lyme disease proteins has led to the development of a rapid, highly accurate diagnostic test for the disease, recently granted approval by the Food and Drug Administration.

Reference: Li, H.; Dunn, J. J.; Luft, B. J.; Lawson, C. L., "Crystal structure of Lyme disease antigen outer surface protein A complexed with an Fab," Proceedings of the National Academy of Sciences USA, 94, 3584-3589 (1997).

Kumanan, D. Eswaramoorthy, S.; Luft, B.J.; Koide4, S.; Dunn, J.J.; Lawson, C.L.; Swaminathan, S., "Crystal structure of outer surface protein C (OspC) from the Lyme disease spirochete, Borrelia burgdorferi," EMBO Journal, 20, 971-978 (2001).

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