Chronic Fatigue Syndrome News: Structure of Lyme Disease Protein Determined
September 10, 2003
[Editor’s Note: This article was received thanks to the Co-Cure moderators. Co-Cure included the following introductory note: “This could be of interest to some who have been labeled with CFS but have Lyme disease.”]
(Released 6/19/2002) Scientists have determined the structure of a telltale protein in the Lyme disease bacterium that picks a fight with a patient's immune system and then evades the antibodies sent out to destroy it.
Writing in the June 14 edition of the Journal of Biological Chemistry (JBC), a team of researchers from The Texas A&M University System Health Science Center Institute of Biosciences and Technology (IBT) in Houston, Texas A&M University (TAMU) and The University of Texas Health Science Center at Houston (UT-Houston) describe the protein's structure and likely reasons for its ability to simultaneously provoke and dodge an immune response.
Research on the protein has provided a highly accurate avenue for diagnosing the disease, which can be difficult to recognize in many cases, said co-senior author Steven J. Norris, Ph.D., professor of pathology and laboratory medicine at the UT-Houston Medical School.
Findings also explain in part the tenacity of Lyme disease, which can survive in a host for years if left untreated.
The protein, known as VlsE, is found on the surface of the bacterium. Six regions of the protein do not change as the organism multiplies, while the genetics of six other regions change rapidly and significantly.
Using X-ray crystallography, the research team at the Center for Structural Biology at IBT and TAMU, led by James C. Sacchettini, Ph.D., obtained a detailed structure of the VlsE protein. Sacchettini is professor of biochemistry and biophysics and of chemistry at Texas A&M University, holding the Wolfe-Welch Chair in Science. He is also the director of the Center for Structural Biology at Texas A&M and IBT.
The structure helps determine the precise location in the protein of the variable and invariant portions. This offers important clues as to why the antibodies against the invariant regions are ineffective despite eliciting a strong immune response in more than 90 percent of Lyme disease patients.
The JBC paper showed that the invariant regions are almost completely buried within the protein and are largely inaccessible to antibodies. The six variable regions, on the other hand, lie mainly on the surface and mask the invariant regions from the host defense. These changing areas may allow Lyme disease to stay a step ahead of the host's defenses by confounding the ability of antibodies to bind to VlsE and hence destroy the bacterium.
Lyme disease is a tick-borne illness that can cause fatigue, sore joints, and ultimately can damage the heart and nervous system. Most cases are easily treated with antibiotics. If not treated early in the infection, Lyme disease can have lingering symptoms in about 10 percent of patients even after treatment. The U.S. Centers for Disease Control and Prevention reports 17,730 U.S. cases of Lyme disease diagnosed in 2000, a record high. The disease is concentrated in 12 northeastern states but was found in all but six states in 2000, the most recent year for which statistics are available.
At IBT, Sacchettini, Christoph Eicken, Ph.D., and Vivek Sharma, Ph.D., are managing a program to elucidate the structures of all outer surface proteins that camouflage the Lyme disease bacterium (Borrelia burgdorferi) and confuse the host immune system. "These structures provide a roadmap to the development of new diagnostics as well as effective vaccines," Sacchettini said.
While understanding VlsE's structure has future research applications for illuminating Lyme disease, it has more immediate utility as a diagnostic tool, Norris said. More than 20 percent of Lyme disease victims do not get a distinctive bulls-eye rash at the site of the tick bite.
Some victims simply fail to notice the rash. Common lab tests that measure antibody responses to the entire Lyme disease bacterium can be confounded by previous exposure to the disease and cross-reactivity with other diseases. Using VlsE or a portion of the protein in these tests gets around both of those problems, Norris has found.
Norris' earlier research established the genetic structure of VlsE, connected portions of the protein to Lyme disease's infectivity, and described the antibody response caused by the protein. UT-Houston co-authors include Matthew B. Lawrenz, a graduate student in the UT-Houston Graduate School of Biomedical Sciences, and John M. Hardham, a former post-doctoral fellow in Norris' lab.
The Texas A&M University System Health Science Center provides the state with health education, outreach and research. Its five components, located in communities throughout Texas, are Baylor College of Dentistry, the College of Medicine, the Graduate School of Biomedical Sciences, the Institute of Biosciences and Technology and the School of Rural Public Health.
Source: Texas A&M University System Health Science Center (received via Co-Cure).