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VlsE and Lyme Disease

A Variable Borrelia-specific Protein

Oct 20, 2008 Albert Burchsted

VlsE is a protein that masks the presence of Borrelia from the immune system with variable regions that allow it to escape attack.

Bacteria and viruses are subject to intense attack by the immune systems of their hosts and often marshal elegant strategies to keep from being annihilated. The strategies used by Lyme Borrelia, B. burgdorferi and related spirochetes that cause Lyme disease (LD), are manifold and researchers are just beginning to understand the scope of this bacterium's arsenal. An important component of the Borrelia arsenal is a stealth protein: VlsE.

What is VlsE?

VlsE is a lipid-protein conjugate, found on the cell's outer surface during all Borrelia life stages. It is similar to a lipoprotein of the organism that causes African sleeping sickness.

Unlike most proteins, VlsE is produced in many forms. It is a complicated protein with several variable regions (VRs), and six invariable regions (IRs):

Five IRs serve as roots to lock the protein in the outer membrane of the bacteria.
One, C6, is exposed on the membrane surface and triggers antibody formation.

VlsE Evades the Immune System

Microbial surface proteins that are exposed to the host's immune system usually become targets by which the host eliminates the parasite. When synthesizing VlsE, Borrelia periodically replace the VRs with new sequences. This replacement presents fresh surface antigens, and helps Borrelia remain invisible to the immune system. Within four days of being transferred to a mammalian host, VlsE will be produced with more than one VR suite, reducing the strength of the immune response. In ticks, VlsE does not modify the VRs.

The VRs of VlsE form irregularly shaped loops that lie on the bacterial surface and cover both the invariable roots and surface portions of adjacent proteins, hiding them also from immune cells.

VlsE Antigenic Variation System

The loops containing the VRs are coded by pieces of DNA called antigenic cassettes. In a way similar to an audio or video tape cassette:

The loops can be put into and taken out of the protein.
One loop can be replaced by another loop.

The third image below shows this replacement in a schematic view.

Borrelia have fifteen different VlsE cassettes that can insert into any of the variable regions of VlsE. This interchanging of cassettes allows VlsE to appear as one thousand million billion trillion (that's 1 followed by 30 zeros) different antigens. Similar, but smaller, systems also operate for OSP-A, OSP-B, OSP-C, and other proteins. This heterogeneity allows Borrelia to confuse our immune systems by presenting an astronomical number of different antigens. Researchers are presently trying to determine control of cassettes activation.

The C6 Region

The sixth IR, IR6, of the VlsE protein constantly stimulates a strong immune response. It is possible this presentation is a red herring, or decoy, that misdirects the immune system from less protected sites. When antibodies bind to IR6, they do not damage the bacterium or reduce its effect on the host. It is also possible that VlsE is the protein that allows Borrelia to enter T-cells for the purpose of destroying them.

Since IR6 is invariable and found in all Lyme Borrelia, at all life stages, Dr. Phillipp, of Tulane Medical Center, synthesized this portion of VlsE and used it to devise the C6 ELISA one-step diagnostic test for LD. This test both separates Lyme disease from other conditions more accurately and provides a more consistent identification of the disease than the standard ELISA and Western Blot tests used alone, and about the same as the two used in combination.

How Often is the C6 ELISA Test Used?

The Infectious Diseases Society of America (IDSA) diagnostic criteria, which are used by the majority of doctors, reject use of the C6 test for LD. Rather, they use the two-step ELISA / WB sequence where the WB is prescribed only if the unreliable ELISA test first indicates the possible presence of Lyme disease.

Lyme literate doctors who recognize the limitations of the IDSA criteria usually know about and use the C6 test for diagnosis.

Disclaimer

The information in this article is believed to be accurate and is presented for the sole purpose of informing community members of information pertaining to Lyme Borreliosis. Any and all liability for the content or any omissions, inaccuracies, errors, or misstatements in such information is expressly disclaimed. Because the symptoms of Lyme disease may vary from person to person, if Lyme Disease is suspected, consult a qualified, Lyme disease literate doctor to discuss your symptoms and for medical advice. The author and Suite101.com are not liable for any direct or indirect damages or any damages whatsoever resulting from loss of function, use, data, or profits arising from or in connection with the application of information presented in this article.

The copyright of the article VlsE and Lyme Disease in General Medicine is owned by Albert Burchsted. Permission to republish VlsE and Lyme Disease in print or online must be granted by the author in writing.

The VlsE Protein