Mar. 7, 2001 UPTON, NY -- A research team working at the U.S. Department of Energy's Brookhaven National Laboratory has determined the three-dimensional structure of a key protein on the bacterium that causes Lyme disease. Called OspC, the protein is derived from two strains of the Lyme disease bacterium. This research may lead to a second-generation vaccine that would be more effective than the current one.
The current vaccine is based on another Lyme disease protein, known as OspA, which was previously deciphered at Brookhaven. Both OspA and OspC are outer surface proteins of Borrelia burgdoferi, the bacterium that causes Lyme disease. Researchers from Brookhaven Lab, Stony Brook University's School of Medicine, the University of Rochester Medical Center and Rutgers University will report their findings on the structure of OspC in the March 1, 2001 edition of The EMBO Journal.
Spread by the bite of an infected deer tick, Lyme disease is the most common vector-borne disease in the U.S. Between 1982 and 1996, more than 99,000 cases were reported in the nation. Early symptoms of the disease include a bull's-eye rash and flu-like symptoms. If the disease is not promptly treated with antibiotics, more serious symptoms, including joint and neurological complications, may develop.
To determine the structure of OspC, the researchers used a technique at Brookhaven's National Synchrotron Light Source (NSLS) known as multiple wavelength anomalous diffraction. First, researchers grew crystals of the protein that could withstand the intense x-rays at the NSLS. To make large quantities of OspC, the team used the T7 gene-expression system, which was developed at Brookhaven.
Then the crystal was illuminated with beams of x-rays at different energies, and diffraction patterns were recorded on a detector. With the aid of powerful computers, the researchers then analyzed the diffraction patterns to gain the vital information needed to create an image of the protein structure.
John Dunn, a member of the research team from Brookhaven, explains that the structure of OspC is predominantly helical, and very different from OspA, which is flat. Also, a region on the surface of OspC has a strong negative charge. Dunn says the negatively charged region may be attracted to a positively charged site on the surface of human cells, helping the bacterium to cause infection. This feature is only found in the OspC protein derived from bacterial strains that cause human disease.
The scientists believe that a vaccine based on OspC will be more effective than the current OspA-based vaccine because the OspA protein is only present in the bacteria while they are in the cold-blooded deer tick's stomach, and not in the host. After the tick bites the warm-blooded mammalian host, the injected bacteria produce OspC in the host's bloodstream.
When the host is vaccinated solely with OspA, antibodies to this protein can only kill the bacterium inside the tick if it ingests these antibodies with its blood-meal. If the bacterium finds its way into the host, it changes into several other forms for which the vaccine offers no protection.
In contrast, an OspC-based vaccine would enable the host to make antibodies to kill the Lyme disease bacteria within the host's body.
Another member of the Brookhaven team, Subramanyam Swaminathan, added, "In order to develop an effective OspC-based vaccine, we'll have to know the three-dimensional structures of at least a few variants of OspC, especially those from invasive strains. Since we've solved the structure of OspC based on two infectious strains of the Lyme disease bacterium, we now have a prototype for determining the structure of OspC from other strains."
The U.S. Department of Energy's Brookhaven National Laboratory creates and operates major facilities available to university, industrial and government personnel for basic and applied research in the physical, biomedical and environmental sciences, and in selected energy technologies. The Laboratory is operated by Brookhaven Science Associates, a not-for-profit research management company, under contract with the U.S. Department of Energy.
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