The Leprosy bacteria eats myelin off the nerves
Smallpox eradication impossible?
A Commentator wrote:
``Regarding Lyme disease, there are two camps in the medical community. Camp A says that it is strictly a bacterial problem, and we don't want to look at any autoimmune aspects. Camp B says that Lyme is easily treatable and, after that, it is an autoimmune problem; but we don't want to try anything to fix it.''
Another Commentator wrote:
``There is a basis for a third theory.
I still think that Lyme spirochetes cause some of our neurological problems by eating the myelin off our nerve cells. But in January, 2002, I completed reading "Germs" by Judith Miller and others; and now I think a major component of the attack may be similar to autoimmune disease, but it should be called something like "camouflage" disease.
Among many horrible pieces of information, Miller describes the work of the Russian germ warrior Sergei Popov who has defected to the U.S. Popov's most ingenious trick was to snip out the gene for myelin from a human (or other, e.g. mouse) chromosome, and insert it into a virus, for example smallpox, which the Russians made by the ton after signing the 1972 treaty outlawing germ warfare (hopefully without Popov's insertion).
When exposed to Popov's chimera, the test animals (mice) would develop the viral disease. Those that did not die then developed a one hundred percent fatal multiple sclerosis. Popov also inserted the gene into bacteria which gave the same sequence of events.
In a moment of inspiration, Popov discovered he could infect a bacteria such as plague (the black death) with a virus such as smallpox that contained the gene for making myelin. Now he had a 3-wave weapon: Some of the people exposed to the plague bacteria would survive with antibiotic treatment. On dying, the bacteria would release the virus causing, for example, a second wave of smallpox. Those who survived the smallpox would then die of MS.
How does it work? Apparently the body recognizes the microbe with the myelin on its cell wall and produces antibodies for the myelin. These antibodies then attack the myelin in our nerve cells. Because the antibodes are diluted by attacking the host's nerve cells, the microbe has improved its chance of survival.
Could some microbes have developed this talent for picking up host "surface" genes naturally? It would be a most useful adaptation because the host would be firing indiscriminately at the microbe and its own tissues, reducing the probabilty that the microbe would be hit. The microbe has camouflaged itself.
Of course, it would be of little use to a spirochete living in the cartilage of a knee joint to absorb a gene for making myelin, but it would be most useful for it to absorb a gene for making collagen. Such a microbe would also be camouflaged, and the victim would develop arthritis because of his body's indiscriminate attempt to kill the microbe.''
Commentator 1 wrote:
`` "Blebbing" is fascinating, kind of like a jet dropping flares to attract the incoming missles. The blebs are left wherever they were dropped and should be able to continue an antigen response.
This is a play on what you're talking about: ''
ARTICLE from The Scientist, Vol:10, #14, pg.13, July 8, 1996, 1996, By Karen Hopkin
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``Searching The Surface
... Many researchers believe that the secret to B. burgdorferi's infectivity and inflammatory capacity lies in the interaction of its surface proteins with the host's immunological system.
Yale researcher Stephen Barthold, a veterinarian and professor of comparative medicine who developed the first mouse model of Lyme disease, studies the expression of B. burgdorferi surface proteins throughout various stages of the spirochete's life cycle.
He finds that during the early stages of infection, B. burgdorferi avoids immune detection by decreasing its expression of surface proteins or cloaking its expressed surface proteins under a layer of slime. "It's using some sort of stealth-bomber-type mechanism," he says. Or, using another diversionary tactic called blebbing, the spirochete can pinch off bits of its membrane in order to release its surface proteins.
Explains Barbour: "It's like a bacterial Star Wars defense program," in which released surface proteins might intercept incoming host antibodies, keeping the spirochete safe from immunological attack ...''
ARTICLE from Infection 2001 Dec;29):315-9, By Brorson O, Brorson SH, Henriksen TH, Skogen PR, Schoyen R., Dept. of Microbiology, Vestfold Sentralsykehus, Tonsberg, Norway.
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``Association between multiple sclerosis and cystic structures in cerebrospinal fluid.
BACKGROUND: The aim of the study was to search for infectious agents in the cerebrospinal fluid of patients with multiple sclerosis (MS).
PATIENTS AND METHODS: cerebrospinal fluid from ten patients with the diagnosis relapsing remitting MS and from five controls without MS were examined by transmission electron microscopy, dark field microscopy, interference contrast microscopy and UV-microscopic examination of acridine orange staining (AO). All cerebrospinal fluid samples from patients and controls were cultured.
RESULTS: Cystic structures were observed in cerebrospinal fluid of all ten patients by AO and transmission electron microscopy. dark field miscroscopy revealed eight cyst-positive patients out of nine. One of five control persons had such structures in the cerebrospinal fluid; this person had suffered from erythema migrans. Spirochete or rod-like structures emerged after culturing two of the MS patient cerebrospinal fluid samples and these structures could be propagated.
CONCLUSION: A significant association of cerebrospinal fluid cysts and MS was identified in this small study among residents in a coastal area of southern Norway. The cysts could be of spirochetal origin. Our study may encourage other researchers to study larger patient groups.''
ARTICLE from APMIS 2001 May;109(5):383-8, Gruntar I, Malovrh T, Murgia R, Cinco M., Institute of Microbiology and Parasitology, Veterinary Faculty, Ljubljana, Slovenia. email@example.com
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``Conversion of Borrelia garinii cystic forms to motile spirochetes in vivo.
Cystic forms (also called spheroplasts or starvation forms) and their ability to reconvert into normal motile spirochetes have already been demonstrated in the Borrelia burgdorferi sensu lato complex.
The aim of this study was to determine whether motile Borrelia garinii could develop from cystic forms, not only in vitro but also in vivo, in cyst-inoculated mice.
The cysts prepared in distilled water were able to reconvert into normal motile spirochetes at any time during in vitro experiments, lasting one month, even after freeze-thawing of the cysts. Motile spirochetes were successfully isolated from 2 out of 15 mice inoculated intraperitoneally with cystic forms, showing the infectivity of the cysts.
The demonstrated capacity of the cysts to reconvert into motile spirochetes in vivo and their surprising resistance to adverse environmental conditions should lead to further studies on the role and function of these forms in Lyme disease.''
ARTICLE from Nature, 22 February 2001, By TOM CLARKE
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``Comparing the gene sequence of M. leprae with that of its close relative M. tuberculosis which causes TB, [M. tuberculosis is an aerobic, non-motile, rod-shaped bacterium], Stephen Cole of the Pasteur Institute in Paris and colleagues found that over millennia the leprosy bacterium has undergone major 'reductive evolution' -- losing genes and therefore the ability to adapt ...
Leprosy has been largely absent from Europe since the fourteenth century, but as many as 700,000 new cases of the disease still occur each year, mostly in the developing world ...
Unlike most invaders, M. leprae can withstand the body's shock troops. In the initial stages of infection, the bacteria are engulfed by white blood cells but they are not destroyed. Instead, the blood cells unwittingly carry the bacteria to their new home inside cells known as macrophages, which are also part of the body's immune response. Here, the bacteria invade certain types of nerve cell, eventually causing the skin lesions and loss of sensation so characteristic of leprosy ...''
ARTICLE from Science, published by The American Association for the Advancement of Science, By Peter J. Brophy
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Volume 296, Number 5569, Issue of 3 May 2002, pp. 862-863.
``MICROBIOLOGY: Subversion of Schwann Cells ...
The authors RULE OUT INVOLVEMENT OF THE IMMUNE SYSTEM IN THE NERVE DEMYELINATION CHARACTERISTIC OF LEPROSY.
They infected the peripheral nerves of Rag1-deficient mice with M. leprae. These mice lack both B cells and T cells of the immune system, and so they cannot mount either a humoral or a cell-mediated immune response to bacterial infection.
Demyelination induced by the bacillus was just as effective in these immune-deficient mice as in animals with a normal immune system. The authors reasonably conclude that binding of bacterial PGL-1 to a-dystroglycan on the surface of myelinating Schwann cells is sufficient ...
CHRONIC EXPOSURE of peripheral nerves to M. leprae could prevent remyelination by stalling Schwann cell differentiation and increasing the available pool of cells susceptible to colonization.
Both the loss of myelin and the block in remyelination would contribute to the death of axons. It is now appreciated that the severe damage observed in a variety of human demyelinating peripheral neuropathies is the result of axonal damage attendant on the loss of the myelin sheath ...''
REPORT from THE ROCKEFELLER UNIVERSITY
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Issued: November 13, 2000
``Researchers Find How Leprosy Bacterium Selects and Attacks Nerves
Mode of invasion may provide clues to the early events of other neurological diseases
Researchers at Rockefeller University who study the bacterium that causes leprosy say they have identified a component on the microbe's surface that allows it to specifically select and attack the peripheral nerves.
The finding clarifies how the bacterium, Mycobacterium leprae (M. leprae) precisely seeks out peripheral nerves, and it sheds light on the early stages of nerve damage in other neurodegenerative diseases such as Guillain-Barre syndrome and MULTIPLE SCLEROSIS.
"If we can understand what neural cell molecules the bacteria use to infect the nerves, we'll gain more insight into what kinds of signaling pathways are involved in bacterial-induced nerve degeneration," says Anura Rambukkana, Ph.D., principal investigator and research associate in the Laboratory of Bacterial Pathogenesis.
In addition, learning what M. leprae does to perturb neural signaling may help researchers understand how the pathway normally works, a process that is still poorly understood. The research was reported in the Oct. 27 issue of the journal Cell by Rambukkana together with Vincent Ng, a graduate student at Rockefeller, and researchers at three other institutions ...
The peripheral nervous system consists of all the nerves that fan out from the brain and spinal cord and includes the muscles, skin and internal organs.
|During development, Schwann cells encase nerve fibers and wrap around the axon to form the myelin sheath. This sheath greatly improves the reliability and speed of the electric impulse, much like insulation on electrical wires.|
WHEN MYELIN IS DAMAGED, AS with M. leprae infection and IN PATIENTS WITH Guillain-Barre syndrome and MULTIPLE SCLEROSIS, the nerve fibers are no longer insulated and nerve impulses cannot be conducted efficiently.
The Schwann cell-axon unit is surrounded by an outer layer called the basal lamina, a matrix secreted by the Schwann cells. The components of the basal lamina that are targeted by M. leprae play a vital role in myelination.
Rambukkana and colleagues previously reported that a major component in the Schwann cell basal lamina, called lamina-2, and its receptor, called dystroglycan, are involved in M. leprae's interaction with Schwann cells. This interplay allows the bacterium to infect the peripheral nerves, which eventually causes nerve damage.
The new research focuses on the invader's side of the interaction, specifically, on identifying the part of the microbe's cell wall that allows the interaction to occur.
The cell wall of M. leprae is endowed with large quantities of a glycolipid called phenolic glycolipid (PGL-1). PGL-1 contains a trisaccharide unit that exists only in M. leprae. This uniqueness led researchers to speculate that PGL-1 plays an essential role in functions that are specific to the leprosy bacterium, such as infecting peripheral nerve cells, but they had no proof ...
Now the researchers have demonstrated that PGL-1 binds specifically to native laminin-2 but not to other proteins in the basal lamina of the Schwann cell-axon unit. It turns out that invasion of the Schwann cell is ultimately controlled by the neural target, not the invading microbe.
The basal lamina is a dynamic action zone that functions to instruct neural cell phenotypes and activation. Modulation of the basal lamina has profound effects both on its function and the consequent behavior of cells residing within it. Therefore, it is not surprising that the basal lamina and Schwann cells respond to PGL-1 upon contact with the bacterium by opening the pathway to allow the intruder to enter ...
"We think clarifying PGL-1's role in nerve infection will eventually make it possible to develop strategies to block bacterial invasion of the peripheral nerve cells at an early stage and thus prevent neurological damage before the immune system gets involved," Rambukkana says.
Leprosy is a chronic bacterial infection that damages nerves, mainly in the limbs and facial area, and also leads to skin lesions.
M. leprae is the only known human bacterial pathogen that attacks the Schwann cell of the peripheral nervous system, and the nerve damage it induces is by far one of the leading cause of peripheral nerve disease in the world. [Has any research been done to determine if the Lyme spirochete attacks the Schwann cell?]
The disease can be treated ith multidrug therapy that kills most of the M. leprae in a few weeks. However, nerve function loss caused by M. leprae invasion of Schwann cells is irreversible.
Rambukkana and his colleagues are now focusing on how neurotropic pathogens, both M. leprae and viruses, attack the peripheral nervous system, and they hope to use these pathogens and their products as tools to identify early molecular events of neurodegenerative diseases.
The researchers will focus especially on DEMYELINATING DISEASES, both those of infectious origin, known to be caused either by bacteria or viruses, AND THOSE WITH UNKNOWN CAUSES, SUCH AS Guillain-Barre syndrome and MULTIPLE SCLEROSIS ...''
ARTICLE from Science News, Week of July 13, 2002; Vol. 162, No. 2, By John Travis
``Do-It-Yourself: Virus recreated from synthetic DNA
In an experiment with implications for bioterrorism and the worldwide campaign to eradicate polio, scientists have used poliovirus' widely known genetic sequence to synthesize that virus from the building blocks of DNA and a broth of other chemicals.
"It's the first time someone has started with a sequence on paper and put together the necessary ingredients chemically to create the virus specified," says Eckard Wimmer of the State University of New York at Stony Brook, who led the work. "We don't need any nature-formed template anymore. We just need the Internet to tell us the sequence of a virus. You can make pretty much any virus this way."
"Scientifically, the results are not surprising or astounding in any way," says virologist Vincent Racaniello of Columbia University. "The point here, of course, is that the DNA can be synthesized from the [genetic] sequence, and this could be done by any third-rate terrorist." ...
Wimmer and his colleagues used common laboratory machines to synthesize DNA strands harboring the same protein-encoding instructions that a typical poliovirus carries ...
Wimmer, Racaniello, and other scientists suggest that the new findings could make it pointless to destroy the last few stockpiles of viruses such as smallpox. "The sequence [of the smallpox virus has been published and is available. It's a difficult virus to recreate, but it will be possible," says Wimmer ...
"In the posteradication era, we must always have plans for what to do in the event that the virus reappears, whether by accident or by evil intent," Racaniello says. "Unfortunately, and frighteningly, there are no such plans at hand."''
Cello, J., A.V. Paul, and E. Wimmer. In press. Chemical synthesis of poliovirus cDNA: Generation of infections virus in the absence of natural template. Science. Abstract available at http://www.sciencemag.org/cgi/content/abstract/1072266v1
Nomoto, A., and I. Arita. 2002. Eradication of poliomyelitis. Nature Immunology 3(March):205.
Racaniello, V.R. 2000. It is too early to stop polio vaccination. Bulletin of the World Health Organization 78(March):359-360. See http://www.who.int/bulletin/pdf/2000/issue3/round.pdf.
Vincent R. Racaniello
Department of Microbiology
Columbia University College of Physicians and Surgeons
701 West 168th Street
New York, NY 10032
Department of Molecular Genetics and Microbiology
School of Medicine
State University of New York at Stony Brook
Stony Brook, NY 11794
From Science News, Vol. 162, No. 2, July 13, 2002, p. 22.