|February 28, 2001|
Brookhaven Scientists Determine Key Lyme Disease Protein Structure
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.
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.
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.
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
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.
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.
an OspC-based vaccine would enable the host to make antibodies to kill
the Lyme disease bacteria within the host's body.
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