Alternative Medicine 2001; September: 60-70.

Mycoplasmas:
The Missing Link in Fatiguing Illnesses

by Michael Guthrie, R.Ph.

These mysterious microorganisms can play a major role in a wide range of diseases including rheumatoid arthritis, chronic fatigue and fibromyalgia syndromes, multiple sclerosis, Gulf War Illness, Crohn’s disease and other inflammatory bowel diseases, diabetes and even aggressive cancers. Without proper diagnosis and treatment of mycoplasma infections, curing these conditions can be difficult or impossible.
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Staff Sergeant Sharron Nicolson, Crew Chief of an Army Blackhawk helicopter, was happy to see everyone return safely from their last deep mission into Iraqi territory. She and her unit would soon join the thousands of U.S. military personnel headed home from the Gulf War, and Sharron was looking forward to finishing her pilot training. But shortly after returning to the U.S. in 1991, Sharron began experiencing constant fatigue, muscle and joint pain and other debilitating symptoms similar to those associated with Chronic Fatigue Syndrome (CFS). She found it impossible to meet the demands of flight school and sadly realized her dream of a flying career was over.

When routine medical tests revealed no answers, Sharron started looking for more help. At the time, she was unaware that over 50,000 soldiers had returned from the Gulf War with similar symptoms. (This number has now grown to over 100,000.) Fortunately, Sharron had the advantage of being the daughter of two top researchers in molecular and cellular biology: Drs. Garth L. and Nancy L. Nicolson. 
At the time of Sharron’s return home in the early 1990s, Garth Nicolson, Ph.D., was an esteemed researcher and academic, holding the David Bruton Jr. Chair in Cancer Research at the University of Texas M. D. Anderson Cancer Center.  Nancy Nicolson, Ph.D., a former instructor in the Department of Immunology and Microbiology at Baylor College of Medicine, was also a world-renowned molecular biologist. The Nicolsons were compelled into action on behalf of their stepdaughter and other veterans whose disabling symptoms were being misdiagnosed as post-traumatic stress disorder and/or other conditions.
The Nicolsons realized that Sharron was experiencing similar symptoms to what Nancy had experienced years earlier.  The cause of Nancy’s pain and fatigue had finally been diagnosed as an infection of invasive mycoplasmas.  The Nicolsons knew these little-known microscopic masters of hide-and-seek were generally responsive to certain antibiotics.  They recommended that Sharron be placed on a course of doxycycline therapy, and she dramatically improved.
 Word spread and members of other Airborne and Special Forces Units who had similar symptoms began asking for assistance. The Nicolsons, anxious to help, began researching what soon became known as Gulf War Illness (GWI).  However, it didn’t take long for them to realize that there was a significant overlap in the symptoms of GWI, Chronic Fatigue Syndrome (CFS), also known as Chronic Fatigue Immune Dysfunction Syndrome (CFIDS), Fibromyalgia Syndrome (FMS), and other conditions that fall under the umbrella term of “fatiguing illnesses.” 

Mysterious Parasites
Mycoplasmas are the smallest self-replicating organisms known to science.  Viruses are even smaller, but they lack the genetic machinery to self-replicate. There are hundreds of types of mycoplasmas that can be found in plants, insects and animals, but only a few can be found in the blood and tissues throughout the human body.  Not all mycoplasmas found in humans are pathogenic (disease-causing). 
Mycoplasmas have among the simplest genomes among bacteria.  The best-known pathogenic mycoplasma, M. pneumoniae, the cause of “walking pneumonia,” contains only 677 protein-coding gene sequences (by comparison, E. coli contains about 4,000).  Mycoplasmas do not contain the genes needed for amino and fatty acid and vitamin synthesis, thus they need to steal certain amino acids, fats, vitamins and other nutrients from host cells in order to survive.   Simply put, they are parasitic bacteria.   Garth Nicolson, now of the Institute for Molecular Medicine in Huntington Beach, California, explains, “Once in the cell, they steal lipids (fats) like cholesterol from the mitochondria, the components of a cell that produces energy.   This makes the mitochondria ‘leaky,’ and they lose electrons.  This is similar to a battery running down when the insulation around the battery is removed.   This may be why patients with intracellular pathogenic mycoplasmas are almost always fatigued.  They have run their cellular batteries down, so that less high energy molecules are available, and they are exhausted at the cellular level.”

Immune Disruption
Mycoplasmas can also disrupt the normal orchestration and organization of the host’s immune system.  They can cause lymphocytes (white blood cells that bear the major responsibility of the immune system) to secrete inflammatory cytokines (proteins that facilitate cell-to-cell communication), which leads to swelling, inflammation and either stimulation or suppression of the immune system.
Because pathogenic mycoplasmas leaving a cell they have infected can incorporate much of the host’s cell surface material into their own surface structure, they can instigate an autoimmune response in which the immune system starts attacking the host’s own cells, a process that can result in severe tissue damage and pain. Meanwhile, the mycoplasmas evade the immune system by hiding inside host cells or fusing with the cellular membrane of the host cells. Certain pathogenic mycoplasmas can also invade lymphocytes and disrupt their functioning without provoking an immune response. Using a trick known as “molecular mimicry,” mycoplasmas can even closely resemble host structures to fool the immune system into thinking that they are normal host cells.
After invading host cells, mycoplasmas can trigger the release of “reactive oxygen” free radicals that modify the RNA and DNA of the cells, an event that can eventually leading to malignant transformation.  This phenomenon has been observed in a laboratory study in which benign (non-cancerous) cells infected by mycoplasmas became irreversibly malignant (cancerous) after 18 cell divisions.  Dr. Nicolson has been working with two colleagues, Drs. Darryl See and Ferre Akbarpour, of the Immune Institute in Huntington Beach, California.  Their research has found that nearly 90% of certain late-stage cancer patients show infection with pathogenic mycoplasmas. These mycoplasmas appear to drive the progression of cancer cells, making them more malignant and metastatic (capable of spreading throughout the body).
Mycoplasmas can also invade the lining of blood vessels, where they appear to facilitate the release of biochemicals that can cause vasculitis (inflammation of blood vessels due to infection) and the formation of plaque inside blood vessel wall surfaces.

Smart and Slinky
Mycoplasmas are well equipped to play biological slight of hand, appearing then disappearing, changing shape, shuffling their surface components, ducking into cells, then parading as normal citizens of the human flora dressed in clothes stolen from the cells they invaded.  They’re elusive because they are pleomorphic (structurally changing).  They do not have rigid cell walls like most bacteria; instead they possess fluid lipid outer surfaces, and like tiny jellyfish, they can squeeze, bend and move into tight spaces.  They can also slide right through laboratory and hospital filters used to produce or maintain sterility— making them one of the most common contaminants in diagnostic laboratories and vaccine manufacturing.  In one recent study of vaccines, mycoplasmas were found to contaminate about 6% of commercial vaccines.
These microorganisms have been quite successful in adapting to many environments; infecting everything from insects to elephants, plants to people.  Generally speaking, they are species-specific, but there appears to be many exceptions.  Garth Nicolson relates more than one case in which the pets of GWI or CFS patients were exhibiting similar symptoms as their owners, and then tested positive for the same mycoplasmas.  No one knows for sure how contagious mycoplasmas are, but it appears that transmission may occur among infected people in close proximity for extended periods of time.  Of course, not everyone who is exposed becomes sick. For example, when Nicolson studied Gulf War veterans’ families who became sick with symptoms similar to GWI, he found that not every member of the family became sick, but those that did become ill had the same infection as found in the sick veteran.

Detecting Mycoplasmas
 When the Nicolsons began to explore the connection between GWI and mycoplasma, they first had to figure out how to screen people with GWI signs and symptoms for the presence of these pathogens.  This was easier said than done.  Since mycoplasmas are extremely small, change shape and lack rigid and distinctive cell walls, they’re impossible to find using conventional microbiology techniques.  They won’t grow in a standard culture medium, and they are not usually revealed by standard tests that look for antibodies (proteins made by a white blood cell as a primary defense against foreign substances). Some people do show antibody responses to certain mycoplasmas, but antibody tests are still not specific enough to make a diagnosis.
Using a technique called nucleoprotein gene tracking developed by the Nicolsons they were able to identify mycoplasma genetic elements in white blood cells of GWI patients.  However, conventional Polymerase Chain Reaction (PCR) tests performed by Army pathologists did not confirm the presence of mycoplasma DNA.  Eventually, the Nicolsons developed a new PCR test based on techniques used by forensic pathologists to test for DNA from crime scenes.  This test revealed that over 40% of the GWI patients were positive for “invasive” mycoplasmas (not mycoplasma in superficial sites such as nose, throat and genitourinary tract).  
The Nicolsons found mycoplasmas, especially M. fermentans, inside tissues and in certain white blood cells—the very cells that are normally involved in the destruction of pathogenic invaders. “Mycoplasmas are not found systemically in most normal subjects—only a few percent of asymptomatic subjects have evidence of mycoplasma in their blood.  I don’t consider oral mycoplasma, or mycoplasma at other superficial sites to be evidence of an infection.  It is more likely simple bacterial colonization, and unless these mycoplasma invade the epithelial cell layer (a thin layer of tissue that covers a surface or lines a cavity), they are probably benign nonpathogenic residents,” explains Garth Nicolson.
The researchers’ results were significant and published in several journals. Other investigators, especially those working with Gulf War Vets, were able to duplicate the results, but the Nicolson’s work was largely dismissed or ignored by the Department of Defense.  However, in February 2000, psychiatrist Lt. Col. Charles Engel, M.D., director of the Gulf War Illness Center at Walter Reed Army Medical Center, presented pivotal information to a Chronic Fatigue Syndrome (CFS) coordinating board at the National Institutes of Health (NIH).  A study conducted independently for the U.S. Departments of Defense and Veterans’ Affairs demonstrated that approximately 40% of more than 1,600 GWI patients were positive for mycoplasma infections, and 80% of those were positive for M. fermentans.  Lt. Col. Engel also stated that he felt that these infections might also be an important cause of CFS.  The study findings nearly duplicated the figures that the Nicolsons had reported earlier: 45% positive for mycoplasma; 80% with M. fermentans.
Currently, other prominent researchers are corroborating the role of mycoplasmas in disease. The number of known conditions in which mycoplasmas play a role is growing, thanks to advances in detection.  Mycoplasmas are now said to be contributors, or at least cofactors, in many conditions, including CFS/CFIDS, fibromyalgia syndrome (FMS), lupus, multiple sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), psoriasis, scleroderma, Crohn’s disease, solid cancers, leukemia, lymphoma, pelvic inflammatory disease (PID), asthma, atypical pneumonia, Sjogren’s syndrome, interstitial cystitis and Alzheimer’s and cardiovascular diseases.  Mycoplasmas have also been associated with autoimmune diseases that can cause definite changes in nerve conduction, demyelation (a degenerative process that erodes away the myelin sheath that normally protects nerve fibers) and sensitivity. 
Dr. Garth Nicolson says that the role of mycoplasmas in various illnesses and diseases is now gradually being accepted, especially in those once long-suspected as being “psychological.” Acceptance is due to the recognition that symptoms cannot be explained solely by psychological criteria and because discrete clinical markers have been discovered.  For example, the vasculitis (inflammation of blood vessels) found in mycoplasma-positive patients correlates with evidence of mycoplasma-induced abnormalities in blood cells and proteins related to blood clotting. 

Current Mycoplasma Research 
Recently, Garth Nicolson has focused on various autoimmune neurological diseases such as ALS, MS, Lyme disease and others.  For example, in ALS (commonly known as Lou Gehrig’s disease) patients, approximately 85% are positive for systemic mycoplasma infections, and most of these involve M. fermentans and/or M. hominis.
Dr. Nicolson is working closely with Drs. See and Akbarpour on ALS, a condition in which patients lose control of their motor and skeletal muscles over a period of two to five years. Their research revealed that almost all ALS patients have co-infections with a virus from the enterovirus family (a virus related to the polio virus that replicates mostly in the gastrointestinal tract) and mycoplasmas. The three doctors have been conducting a clinical treatment study of ALS utilizing antibiotics, antivirals and nerve growth factors.  They are seeing positive results so far, as measured by increases in muscle strength.
Other illnesses often have multiple strains of mycoplasmas, or mycoplasmas combined with co-infections of other bacteria or viruses. “In recent published studies from our laboratory, most CFS and FMS patients had multiple mycoplasmal infections in their blood. The number of different mycoplasmal species in these patients increased with the number of years the patients were sick and with the severity of their illness,” says Dr. Nicolson.
“We have found that when the few asymptomatic subjects have blood mycoplasmal infections, they have only one species, versus when we examine patients who are sick with various chronic illnesses, they usually have multiple species of mycoplasmas and other infections such as the viruses HHV-6 or CMV. In Lyme disease, we often find mycoplasmal co-infections, most frequently, M. fermentans, along with the Borrelia that causes it. This makes sense when you consider that insects, such as the ticks that carry the Borrelia, also can carry mycoplasmas.  Dr. Eli Mordechai of Medical Diagnostics Lab of New Jersey has exactly the same findings in Lyme disease patients.” 
 All the researchers above agree that long-term antibiotics must be initiated to treat mycoplasmal infections.  Additional strategies must be applied to protect and strengthen the immune system and provide essential nutrients and vitamins. “We always try to use the least toxic approaches in working with pathologies, so we use a lot of natural products,” Dr. See says.  For example, probiotics and non-denatured whey protein isolates are used to support the GI tract—a combination that helps prevent overgrowth of undesirable microorganisms. “However,” adds Dr. See, “in our experience, and in the literature, we have found no other way to deal with mycoplasmas than fairly long-term treatment with certain antibiotics.” Fortunately, the Nicolsons and their colleagues have succeeded in helping many veterans and others infected with mycoplasmas, but controversies surrounding their work and these mysterious microorganisms still persist.
Says Dr. Nicolson “Future efforts to explain and treat a variety of chronic illnesses that currently have unknown etiologies (causes) will undoubtedly focus more on chronic infections as underlying causes or as opportunistic infections in immune impaired patients.  We have found that chronic infections caused by mycoplasmas, viruses and other microorganisms cannot be ignored, because these patients will remain ill and not recover from their illnesses if these infections remain untreated.”

Diagnostic Testing for Pathogenic Mycoplasmas
So what do you do if your suspect you are infected with mycoplasmas?  You should be tested by a certified clinical laboratory equipped with the specialized molecular tests to find pathogenic mycoplasmas.  You should also be tested for other organisms, i.e., bacteria and viruses, associated with these chronic diseases.  The Nicolson have developed a battery of tests for patients suffering with the diseases mentioned in this article.  These tests must be ordered by your physician.  The Nicolson maintain two websites.  The website for the certified reference laboratory, International Molecular Diagnostics is www.imd-lab.com; telephone number 714-799-7177. The Institute for Molecular Medicine website is www.immed.org.  Here you will find publications and documents on CFS, FMS, autoimmune diseases and other chronic illnesses.  Immediate fax-back information is available 24 hours a day by calling 714-903-2900.

Contact:
Additional information on mycoplasma treatment, yeast overgrowth, nutrition and treating multiple infections associated with mycoplasmas can be found on the Institute for Molecular Medicine’s website (www.immed.org).

About the Author:
Michael Guthrie R.Ph. is a clinical pharmacist with hospital, business and residential experience, who began researching scientifically validated integrative medical approaches. For the last few years, he has worked as a free-lance medical writer and consultant involved in the development of print, web and video for the integrative-medical community.