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Mycoplasmas: What enables them to cause disease?

In the 50 years that Thomas McPherson Brown, MD researched mycoplasma as a potential cause of arthritis, he was hampered by the technology of his day. It is this new technology which is now validating his work with mycoplasma and keeps it as a prime candidate as a cause of arthritis.

Used in the broad sense, arthritis is a complex disease which is probably not caused by one organism, but will rather turn out to be a complex reaction to many things: genetics, environment, and organisms - mycoplasma among them.

Belonging to the class Mollicutes (mollis - soft and cutis - skin), mycoplasmas lack a cell wall but instead are surrounded by a soft membrane. Sometimes thought of as obscure, harmless organisms, these tiny microbes have been discovered to be developmentally advanced, complex organisms fully capable of causing serious and chronic disease either by themselves or as cofactors.

"Infection often precedes the onset of autoimmune disease" September 1993 Scientific American. D. K. Ford elaborated, explaining "An individual's arthritis is caused by his/her abnormal immune response to a particular infectiouis agent."

The case for a microbial cause of rheumatic disease has been investigated since the 1930's by Gail Cassell, Barry Cole, Alan Cantwell, Thomas McP. Brown, David Taylor-Robinson, Graham Rook, Garth Nicholson, Aristo Vojdani, T. Schaeverbeke, Emil & William Wirostko and many others. Their work has appeared in medical journals continuously for many decades. Despite this continuous evidence and despite the fact that many forms of animal arthritis are acknowledged to be caused by a mycoplasma, the application of mycoplasma as a cause of human arthritis is considered unproven. This might be due to the belief that a joint disease such as rheumatoid arthritis would have to have organisms in the joint if those organisms were the cause of the disease. In fact, mycoplasma have been found in the joints of RA patients. I

It is the unique properties and amazing adaptability which make mycoplasma a particularly formidable adversary.

I. Properties of mycoplasma

Mycoplasmas are able to cause serious and chronic disease because of some unique characteristics.

They prey on individuals with weakened immune systems. Those individuals are particulaly susceptible to mycoplasma infection.

Mycoplasmas are able to hide inside the cells of the host (patient).

They depend on the host for nutrients such as cholesterol, amino acids, fatty acids, etc.

A mycoplasma does not have its own DNA, but is capable of using the DNA from a cell which it has penetrated, causing that cell to malfunction and die.

Mycoplasmas have the ability to compromise natural and necessary but harmless bacteria which protect us from disease and help our body to function (such as the friendly bacteria in the intestine which aid digestion).

They are highly adaptable to changing environments

They can cause serious, chronic disease alone or as co-factors as in AIDS, Gulf War Illness, Chronic Fatigue Syndrome and Chron's Disease'

They can be difficult to treat, requiring long-term therapy.


"The eradication of these pathogenic mycoplasmas from various tissue sites requires an intact and functional immune system, although persons with fully competent immune systems may have difficulty eliminating mycoplasma, even with recommended prolonged drug therapy." Baseman & Tully 


II. Which Disease Develops Depends on A Number of Host Cell Responses

Which mycoplasma is the infecting one?

the number of mycoplasmas which are able to attach to host cells

the length of incubation (time)

Whether stimulation of pro-inflammatory cytokines (chemical messengers of the immune system) takes place

the age and strength of the immune system of the host (patient)

Sometimes there are symptoms which accompany infection; sometimes there are no evident symptoms.

"Differences in disease severity from patient to patient may relate to the effectiveness of the immune system in eliminating particular mycoplasma strains."'

III. How Mycoplasmas Cause Disease

Mycoplasmas have arms with hooked tips on which they display proteins called adhesion proteins. These proteins enable them to adhere or attach firmly to targeted host cells. Their favorite environment for colonization is mucous membranes. A person with a weak immune system would not be able to make antibodies which could block the mycoplasma's ability to attach to and invade host cells.

For example: one of the favorite places of mycoplasma is the mucous membrane in the respiratory tract. Mycoplasma needs cholesterol for membrane function and growth, and there is an abundance of cholesterol in the bronchial tubes of the respiratory tract. This large amount of cholesterol in the membrane surrounding the mycoplasma may affect interaction with the immune system's phagocytes (white blood cells).'

Mycoplasmas are able to attach to the outer membranes of phagocytes and impair the ability of those very phagocytes to kill other harmful bacteria such as E coli.

Mycoplasmas are even able to live inside the very phagocytes that are supposed to kill them and thus may be carried to new locations of inflammation hidden away like a spy who has infiltrated the defending army.

The mycoplasma adhesion proteins are strikingly similar to human proteins. This mimicry or copying by the mycoplasma can perhaps be responsible for the body's apparent attack on itself - something which has been called autoimmunity.

There is a relationship to other organisms such as strep. Antistrep antibodies can cross-react with or attack body tissues such as the heart tissue or mycoplasma adhesion proteins.

The mycoplasma then protects itself with a protective coat of proteins which signal the host's body to activate an immune system response which is often inflammatory in nature. Thus, a human mycoplasma infection would be consistent with autoimmunity and inflammatory diseases.'

When the mycoplasma attaches, it generates hydrogen peroxide and super-oxide radicals which cause oxidative stress and damage to the surrounding tissues.

Mycoplasmas compete with host cells for nutrients which interfere with host cell function.

Mycoplasmas can turn on the chain reaction called an immune system response.

Mycoplasmas are able to avoid immune system defenses which would normally kill disease-causing organisms.

Gaining entrance to the inside of a host cell enables mycoplasma to hide from the immune system attack as well as from some medications, even when treatment is longterm.

IV. Reasons to Test for Specific Mycoplasma Strains

They are difficult to treat. Tetracyclines (tetracycline, minocycline or doxycycline) usually work as does erythromycin, but not with all strains. Mycoplasma fermentans and Mycoplasma hominis strains are usually resistant to erythromycin. Tetracycline resistant strains of M. hominis and Ureaplasma urealyticum also exist.

These antibiotics do not kill the mycoplasma, but rather incapacitate it, leaving it to the strong immune system to deal the killing blow. In cases where the immune system is weak, this killing of the mycoplasma does not occur. The choice of antibiotic and route of administration (oral, IV or injection) can be critical as can the need for prolonged therapy. Therapy should only be altered or discontinued if there is no clinical or microbiological response, and then only with continued observation for a return of symptoms.

References:

I JB Baseman, JG Tully, Mycoplasmas: Sophisticated, Reemeerging, and Burdened by Their Notoriety, Emerg Infect Dis, 1997 3:1.

2 AJ Marshall, RJ Miles, L Richards, The Phagocytosis of Mycoplasmas, J Meds Microbiol, 1995; 43: 239-250.

3 T. Schaeverbeke, et al, Mycoplasma fermentans in Joints of Patients with Rheumatoid Arthritis and Other Joint Disorders, Lancet, May 18, 1996; 347; 1418.