Monday, March 25, 2013

The Complexities of Lyme Disease (Part 3): When Lyme Bacteria Infects the Brain

This is Part 3 of the series, The Complexities of Lyme Disease by Thomas Grier, M.S. Click here to read Part 1 and here to read Part 2. Part 4 is soon to come.  ~ Michelle

When Lyme Bacteria Infects The Brain:

As we have previously discussed, the pathogen that causes Lyme disease is a highly motile spirochete within the Borrelia family of bacteria. This is the same group of bacteria that cause Relapsing Fevers in Africa and around the world. Like other Relapsing Fever bacteria, Borrelia burgdorferi (Lyme bacteria) has both an affinity for the brain and a mechanism to penetrate into it.

While Lyme may be a bit more subtle upon penetrating the brain, its silent but insidious invasion may be the reason that brain involvement can and is often overlooked by physicians for months or even years in neurological Lyme patients.

In the case of Lyme disease, every animal model to date shows that the Lyme spirochete can go from the site of the bite of an infected tick to the brain in just a few days. While we know this bacteria can break down individual cell membranes and capillaries, its entrance into the brain is too pronounced for such a localized effect.

When the Lyme bacteria enters the human body, we react by producing several immune regulatory substances known as cytokines and lymphokines. Several of these act in concert to break down the blood-brain barrier (e.g., IL-6, Tumor Necrosis Factor-alpha, IL-1, Transforming Growth Factor-beta, etc.). In addition to affecting the blood-brain barrier, these cytokines can make us feel ill and give us fevers.

Since the brain has no immune system, it prevents infection by limiting what can enter the brain. The capillary bed that surrounds the brain is so tight that not even white blood cells are allowed to enter. Many drugs can’t enter either, making treatment of the brain especially hard.

For the first ten days of a Lyme infection, the blood-brain barrier (BBB) is virtually nonexistent. This not only allows the Lyme bacteria to get in but also immune cells that can cause inflammation of the brain.

Note: The breakdown of BBB was shown to occur by tagging WBCs, albumin, and other substances known not to cross the BBB with radioactive iodine. The CSF (cerebrospinal fluid) of mice was tested, and then they were infected with Bb (Borrelia burgdorferi). The CSF was then retested every day after for several weeks. The result? No crossover of iodine was present in the control group, but 100% crossover was in the infected group for 10 days. The infection had the same result on the BBB as if you were injecting the radioactive iodine directly into the brain.

Once the Lyme bacteria enter the brain, they continue to divide and become entrenched within the brain's tissues and cells. Borrelia burgdorferi is directly neurotoxic upon contact with neurons and also has a negative effect on glial cells trying to repair brain injury. This, in turn, further increases the permeability of the blood-brain barrier, allowing, even more, blood-borne agents to enter the brain. The immune system responds to the new flood of internal bacterial antigens and produces more inflammatory cytokines. The result can cause brain edema or encephalitis, intracranial pressure, and focal areas of demyelination.

Also, when the human brain becomes inflamed due to infection with the Lyme bacteria, cells called macrophages respond by releasing a neuro-toxin called quinolinic acid. This toxin is also elevated in Parkinson’s Disease, MS, and ALS. What quinolinic acid does is to stimulate neurons to repeatedly depolarize. If this goes on unabated, it eventually causes the neurons to demyelinate and die. Basically, people with elevated quinolinic acid have short-term memory problems.

This means: If we think of our brain cells like telephone lines, we can visualize the problem. If all of the lines coming in are busy, we can’t learn anything. If all of the lines going out are busy, we can’t recall any memories. Our thinking process becomes impaired.

A second impairment to clear thinking that Lymies can experience is the restriction of proper circulation within the blood vessels inside the brain. Using an instrument called the Single Photon Emission Computerized Tomography scanner (SPECT scans), we are able to visualize the blood flow throughout the human brain in 3-D detail. What was seen in the brains of chronic neurological Lyme patients was an abnormal “Swiss-Cheese” pattern of blood flow. The cortical or thinking region of the brain was being deprived of good circulation, while the occipital (eyesight) regions had an increased flow. This could help explain why most Lyme patients complain of poor concentration and overly sensitive eyes.

The Complexities of Lyme Disease (A Microbiology Tutorial) by Thomas Grier, M.S.
Neurocascade Events and Lyme by Thomas Grier, M.S.

Friday, March 8, 2013

The Complexities of Lyme Disease (Part 2): Motility of the Lyme Bacteria

This is Part 2 of the series The Complexities of Lyme Disease by Thomas Grier, M.S. Click here to read Part 1. I'll post Part 3 next week.  ~ Michelle

Motility of the Lyme Bacteria: 

How does the Lyme bacteria travel from the bloodstream to other tissues? While we have known for a long time that the Lyme spirochetes can show up in the brain, eyes, joints, skin, spleen, liver, GI tract, bladder, and other organs, we didn't understand the mechanism by which it could travel through capillaries and cell membranes. Then, Dr. Mark Klempner, M.D., presented at the 1996 LDF International Lyme Conference an interesting paper that gave us part of the answer.

Many researchers have observed that the Lyme spirochete attaches to the tip of the human cells first. It then wiggles and squirms until it enters the cell. What Dr. Klempner showed was that when the spirochete attached to the human host cell, it caused that cell to release digestive enzymes that would dissolve the cell and allow the spirochete to go where ever it pleases. This is very economical for the bacteria to use our own cell's enzymes against us because it does not need to carry the genes and enzymes around when it travels.

Dr. Klempner also showed that the spirochete could enter cells such as the human fibroblast cell (the skin cell that makes scar tissue) and hide. Here the pathogen was protected from the immune system and could thrive without assault. More importantly, when these Bb-fibroblast cultures were incubated with Rocephin (ceftriaxone), two-thirds of the cultures still gave rise to live spirochetes after two weeks and in later experiments for more than 30 days.

If we can't kill it in a test tube at these high concentrations of Rocephin in four weeks, how can we hope to kill it in the human body?

This means: The infection can enter the best tissue that is optimal for its survival. Once it gains an intracellular position, it may evade the immune system and antibiotic therapy by remaining sequestered away from these hostile environs.

Another interesting observation about this bacteria is how it interacts with our body's immune system.

Dr. David Dorward of the NIH Rocky Mountain Laboratories showed that when healthy normal human B-cells were placed in a culture with live Borrelia burgdorferi, it was only a matter of moments before the spirochetes started to attach and penetrate the antibody-producing white blood cells. Once inside the cell, the bacteria should be killed by a process wherein B-cell lysosomal enzymes dissolve the bacteria. But this does not happen. Instead, the bacteria actually thrive and eventually destroy the lymphocyte.

What is much more disconcerting is that by using a time-lapse video camera, the spirochete can be seen to enter the B-cell and exit a short distance later. But when it exits, it appears to be wearing the membrane of the B-cell. The live motile bacteria then swims about unharmed in the sea of B-cells because by wearing the cloak of its enemy, it goes undetected. This stealth-type camouflage will prevent antibodies from attaching to it; it prevents the complement enzymes in the blood from finding and destroying it, and it eludes the scavenger white blood cells such as macrophages and killer T-cells that normally hunt and destroy foreign pathogens.

This means: We have a highly evolved bacteria that is highly mobile, can dissolve any tissue it desires so it can find immune-privileged sites, and can camouflage itself from our own immune system by wearing the membrane of the very cells that are supposed to track it down and kill it. This bacteria seems to have evolved a sophisticated defense mechanism to avoid our immune system.

Lyme bacteria (Borrelia burgdorferi spirochete) in human blood

The Complexities of Lyme Disease (A Microbiology Tutorial) By Thomas Grier, M.S.

Friday, March 1, 2013

The Complexities Of Lyme Disease (Part 1): The Structure of the Lyme Bacteria

I recently came across this fantastic excerpt written by Lyme researcher and lecturer, Thomas Grier, M.S., who was misdiagnosed with M.S. for years when he had chronic relapsing Lyme disease. Sounds familiar to many of us, I know. He is now the Executive Director of Pathology Studies at MIBDEC (Minnesota Insect-Borne Disease Education Counsel), a non-profit organization. He has a background in microbiology and immunology and continues to do research in both the Lyme and M.S. communities. 

The article is so long that I'm breaking it into parts and using excepts that might not be as well known or understood. I found it extremely interesting. While I already knew some of the basic information; it truly helped me better understand the complexities of Borrelia (Bb) and its effect on and within the human body. I felt the need to share it.

Perhaps some of you are familiar with Grier and/or his work. I had previously read his personal story a couple years ago but never knew he had written the manual (Lyme Disease Survival Manual) this excerpt is taken from. 

I'll post Part 2 in a week or so but I've included a link to the full article at the end of this post for those who want to read it in it's entirety now.    ~ Michelle

Excerpts from The Complexities of Lyme Disease 
by Thomas Grier, M.S.

Why is Lyme disease such a mystery? Why does it mimic so many other diseases? Why is it so difficult to detect? The reasons come from the microbiology of the bacteria that causes Lyme. This paper will look at the biology of this bacteria and the consequences of the organism's unique microbiology on human victims.

Lyme disease is caused by a spiral-shaped bacterium known as a spirochete. Diseases that are caused by spirochetes are notorious for being relapsing in nature, difficult to detect, and great imitators of other diseases. Syphilis, Tick-Borne Relapsing Fever, and Leptospirosis are other examples of spirochetal diseases. Lyme disease is caused by a bacteria called Borrelia burgdorferi, named after the man who isolated it from a Deer Tick in 1981, Dr. Willy Burgdorfer. The following is a tutorial to help explain away the mysteries of this bacteria, and why it causes so much controversy between patients and the medical community.

The Structure of the Lyme Bacteria:

The structure of the Lyme spirochete is unlike any other bacteria that has ever been studied before. It is one of the largest of the spirochetes (0.25 microns x 50 microns). It is as long as a fine human hair is thick. Borrelia burgdorferi is a highly motile bacteria. It can swim extremely efficiently through both blood and tissue because of internal propulsion. It's propelled by an internal arrangement of flagella, bundled together, that runs the length of the bacteria from tip to tip.

Like other Borrelia bacteria, Borrelia burgdorferi (Bb) has a three-layer cell wall which helps determine the spiral shape of the bacteria. What makes this bacteria different from other species is that it also has a clear gel-like coat of glycoproteins that surround the bacteria. This extra layer is sometimes called the Slime Layer or S-layer.

This means: This extra layer of glycoproteins (exaggerated in thickness here) may act like a stealthy coat of armor that protects and hides the bacteria from the immune system. The human immune system uses proteins that are on the surface of the bacteria as markers and sends attacking antibodies and killer T-cells to those markers called outer surface protein antigens (OSP antigens). This nearly invisible layer is rarely seen in washed cultures but can be seen regularly in tissue biopsies.

The Lyme bacteria is also different from other bacteria in its arrangement of DNA.

Most bacteria have distinct chromosomes that are found floating around inside the cytoplasm. When the bacteria starts to divide, it forms a new cell wall in the middle and begins to split in two. The chromosomes also divide, and the new copies of the chromosomes enter the new cell. The arrangement of DNA within Borrelia burgdorferi, however, is radically different from other bacteria. It is arranged along the inside of the inner membrane of the cell. It looks something like a net embedded just underneath the skin of the bacteria.

This means: We really don't understand the mechanisms of how Bb regulates its genetic material during its division. The bacterial DNA is uniformly embedded inside the inner membrane of the Bb bacteria, like nylon stocking.

Another unique feature to Borrelia burgdorferi are Blebs. This bacteria replicates specific genes and inserts them into its own cell wall, and then pinches off that part of its cell membrane and sends the Bleb into the host. Why it does this, we don't know? But we do know that these blebs can irritate our immune system.

Dr. Claude Garon of Rocky Mountain Laboratories has shown that there is a precise mechanism that regulates the ratio of the different types of blebs that are shed. In other bacteria, the appearance of blebs often means the bacteria can share genetic information between themselves. We don't know if this is possible with Borrelia species.

There have been reports of a granular form of Borrelia, which can grow to full size, fully autonomous spirochetes and can reproduce. These granules are so small that they can be filtered and separated from live adult spirochetes by means of a micropore filter. The granular/spore form of Borrelia burgdorferi is still being debated. (Stealth Pathogens Lida Mattman Ph.D. 66, Phillips/Mattman 98, Preac-Mursic)

The division time of Borrelia burgdorferi is very long. Most other pathogens, such as Streptococcus or Staphylococcus, only take 20 minutes to double. The doubling time of Borrelia burgdorferi is usually estimated to be 12-24 hours. Since most antibiotics are cell wall agent inhibitors, they can only kill bacteria when the bacteria begins to divide and form new cell walls.

This means: Since most antibiotics can only kill bacteria when they are dividing, a slow doubling time means less lethal exposure to antibiotics. Most bacteria are killed in 10-14 days of antibiotics. To get the same amount of lethal exposure during new cell wall formation of a Lyme spirochete, the antibiotic would have to be present 24 hours a day for 1 year and six months!

If a bacteria is in a non-metabolic state (dormant), no antibiotic is effective. To be lethal, the antibiotic must be absorbed and processed through the bacteria's metabolic machinery and cause a disruption of metabolism.

Unlike antiseptics, antibiotics don't kill on contact. If there are any dormant bacteria hidden in sequestered sites, then regardless of the length of treatment, antibiotics can fail until the bacteria become metabolically active (The Forgotten Plague see reference to Tuberculosis).

Like other spirochetes, such as those that cause Syphilis, the Lyme spirochete can remain in the human body for years in a non-metabolic state. We know this because patients with ACA rash for years are often culture positive when the skin is biopsied and cultured. Non-metabolic bacteria is essentially suspended animation. The bacteria does not metabolize in this state. Antibiotics are not absorbed or effective. When the conditions are right, those bacteria that survive can seed back into the bloodstream and initiate a relapse. It is a beautiful and patient survival mechanism.

This means: Just because a person is symptom-free for long lengths of time doesn't mean they aren't infected. It may simply be a matter of time before the re-emergence of the sequestered non-metabolic bacteria. Whereas viral infections often impart a lifelong immunity and may suppress subsequent relapses or reinfections, Lyme, like other bacterial infections, does not impart an active immunity for a long period of time. People are often reinfected with Lyme. A relapse of symptoms could actually be thought of as reinfection or a reseeding of infection from immune-privileged sites.

The Lyme spirochete has a sequence of surface antigens it can choose to express or not express. There are more than two dozen species of Relapsing Fever Borrelia bacteria that have been clearly identified. We are now beginning to see a similar diversity within the Lyme spirochete family as well. Polymorphism, which is the ability of the bacteria to change its structural identity, makes recognition and identification more difficult. It is like a criminal putting on a new disguise after every time he has committed a new crime.

While there are four generally accepted genospecies of Lyme disease - Borrelia burgdorferi, Borrelia afzellii, Borrelia garinii, and Borrelia lonstarrii - there are hundreds of identified strains of the first three species. Borrelia spirochetes are polymorphic because they have built-in genetic mechanisms to vary their antigens.

This means: Just as the immune system recognizes the bacteria and tries to kill it, the bacteria changes its clothes and fools the immune system, and survives a little longer. Soon the bacteria finds safer areas of the body to hide in, and the immune system stops looking for it. But another aspect of polymorphism is that once the cell changes, it may become even more lethal to some cells. For example, when Borrelia burgdorferi was introduced into the mouse via the bloodstream, the bacteria traveled to the brain. But the bacteria recovered from the brain was more adapted to the brain and could no longer be killed from antibodies in the bloodstream. Polymorphism is a clever way to survive and may offer reasons for multiple symptoms.

The Complexities of Lyme Disease (A Microbiology Tutorial) By Thomas Grier, M.S.

Borrelia burgdorferi (Bb) bacteria (spirochetes) magnified using dark-field microscopy.