By Thomas M. Grier, M.S. ©
Wouldn’t it be nice if, when you’re on safari and you’re charged by a man-eating lion, you knew your gun was loaded with live ammo instead of blanks? I’d like to feel that way when I think about antibiotic treatment of Lyme disease. But what if we’re just shooting blanks? At a recent Lyme disease conference in Detroit, Michigan, that fear of shooting blanks became palpable when I listened to Dr. Lida Mattman, Ph.D., speak about cell wall deficient forms (CWD) of bacterial pathogens, specifically B. burgdorferi, the cause of Lyme disease.
Dr. Lida Mattman, a professor emeritus from Wayne State University, has been studying spirochetes for over fifty years. She was a protégé of the great Gabriel Stiener, who was the first to establish, in a series of papers going back to 1918, that multiple sclerosis was associated in many cases with a spirochete. Since her association with Steiner, Lida Mattman has had a continued interest in spirochetes, but for the last seven years she has focused the bulk of her attentions on cell wall deficient forms.
This area of microbiology has long been neglected, and we are now paying a price for that neglect. Dr. Mattman’s work suggests that cell wall deficient forms are prevalent, and pathogenic. Cell wall deficient forms of a mycobacterium may be thecause of sarcoidosis. Other diseases, such as Crohn’s disease, coronary thrombosis, Kaposi’s sarcoma, endocarditis, and MS, may all involve cell wall deficient bacteria. What were once thought of as anomalies and nonpathogenic are now proving to be insidious, deadly, and nearly invisible. Hence the name of her text book, Stealth Pathogens. (CRC Press) What are cell wall deficient bacteria? First; let’s review some basic microbiology.
For decades, students have been taught that there are three main types of bacteria: rods, spheres, and spirals. These shapes were maintained by a rigid cell wall that added structural integrity to the bacteria. Since human cells don’t have cell walls, a good way to kill bacteria was to interrupt cell wall synthesis, because this would kill the bacteria, but not harm the human host. This is the basis of most bactericidal antibiotics, like cephalosporins (Rocephin, Suprax, Ceftin, Claforan) and penicillin’s (amoxicillin, ampicillin..). The problem is, what happens if there is no bacterial cell wall to inhibit?
When a bacteria like a spirochete loses its cell wall, it becomes incapable of holding its spiral shape. It becomes a sphere surrounded by a thin semi-permeable membrane. This round sphere is like the evil counter pare to the classical spiral form. Why evil? Well, when the bacterium sheds its cell wall, it also sheds several proteins that are markers to the human immune system. In other words, the immune system has trouble finding and recognizing this new form of the bacteria. It’s almost like a criminal using disguises to change identities after each crime. Only this disguise is also bullet proof because, without a cell wall, antibiotics like Rocephin are useless.
What is also intriguing is the fact that these cell wall deficient forms (also known as L-forms) can be seen from time to time as reverting back to the classical form. This means the Lyme spirochete appears to be capable of turning off the genes that create cell walls when it is convenient to do so, and the CWD form can then produce the classical spiral form when it needs to.* Does the bacteria do this to avoid antibiotic therapy? Probably not. It might be an evolved mechanism to dodge mammalian immune systems, but it is doubtful it has specifically evolved a defense mechanism against antibiotics. Survival against antibiotics just happens to be a consequence of this particular evolutionary morphologic development.
This appears to be borne out by some work done over sixty years ago on syphilis patients by Warthin and Olson. It was found that, as you sectioned a blood vessel of a syphilis patient, you found a progression from the classical spiral form to what appears to be the L-forms. As you entered the vessel wall and continued to enter other tissues, the shape of the spirochete gradually changed from a spiral to a sphere. This means that the Lyme spirochete may also favor one form over another, depending on what tissue it is in at the time. This evolutionary strategy makes a lot of sense. If it can survive better in the tissues in a CWD form, then the infection can continue even if its classical spiral counterpart is wiped out and eliminated from the blood stream. In the end, the death of one form of the bacteria is meaningless if the infection is ultimately maintained somewhere else m the host in its alternative form.
Dr. Mattman said she frequently isolates L-forms from Lyme patients with aseptic meningitis and endocarditis, How is this done? Traditional culture media is virtually worthless, as are traditional heat fixed blood smears. The answer is, in many cases, a simple technique that is rarely used any more in labs. A live wet mount is prepared using the patients blood or bully coat. This is a simple procedure, where the blood sample is placed on a wet slide with acrodine orange dye to stain the nucleic acids. Then a monoclonal antibody fluorescent stain that is specific for Borrelia burgdorferi is added. Then the slide is examined under a microscope. Although this is a simple procedure that most labs could easily do; it is not being done. Why? Simply because most labs have no real understanding of CWD forms.
There are some scientists who oppose the idea that CWD forms are the cause of persistent infections. They assert that if CWD forms exist, why can’t we detect them by PCR? Even in absence of cell wall, these bacteria still have to contain DNA. Yet no published studies exist that compare PCR/DNA amplification results to CWD culturing techniques. Although culturing has long since been the gold standard in proof of infection, there seems to be a double standard when accepting culturing as proof when it comes to CWD forms. Unfortunately, both PCR and L-form culture techniques are in their infancy, and are far from perfected or standardized.
Dr. Mattman also has a greater success with culturing the classical forms than most other researchers that I have met. Mostly, this is due to her fifty years of experience with spirochetes, but it also has to do with economics Dr. Mailman is a researcher, and as such, the priority of her lab is not to make money, but to produce data. As a result, Dr. Mattman mixes her own culture media, which is considerably different from the commercially available medias. Since modern hospital labs have long since stopped mixing their own medias, the only medias which are ever used are those which are commercially marketed to the labs through medical suppliers. Since Dr. Mattman’s media is not commercially available, labs will never have the success rate at culturing spirochetes that they should. Labs are in the business of making money, and mixing up media is too hard, too time consuming, and too costly. If it isn’t on the shelf, it’s being used.
More than likely, Dr. Mattman’s culture media will one day be commercially available, but its success has always depended on a couple of freshly made components, so bringing it to market isn’t as easy as it sounds. Although there are better culture medias out there to detect Lyme disease than the commercially available preparations, it is the commercial availability of the other media that wins the day. Thus, modified Kelly media and B 5K-lI are the current standards for culturing the Lyme spirochete.
What does this new information on CWT Borrelia mean to chronic Lyme patients? A medical advisor to Dr Mattman, Dr Steven Philips, MI), suggested that when a patient’s therapy with a bactericidal antibiotic hits a plateau, it may be time to switch to a different regimen of protein inhibitors, such as the combination of doxycycline and Biaxin. These also appear to be the drugs of choice when a patient presents with symptoms of multiple sclerosis. These drugs do not depend on cell division and disruption of cell wall synthesis to kill the bacteria. Instead, they affect bacterial metabolism through inhibition of protein synthesis.
Dr. Mattman made it very clear that a second spirochete has been implicated in causing multiple sclerosis (MS). Her old mentor, Dr. Gabriel Steiner, first isolated spirochetes from MS lesions in 1918, and today the continuation of that work is being pursued by at least three researchers. The suspected organism has been tentatively dubbed Spirochaeta myelophthora.
Since multiple sclerosis is a collection of symptoms of an unknown cause, it is possible that more than one cause will eventually be found. One undeniable fact is that many Lyme patients have been previously diagnosed as having MS. Perhaps Dr.
Mattman’s continued work will someday make that tragedy a rare occurrence!
Are CWD forms responsible for persistent chronic Lyme disease and negative tests? The possibility is quite real, but the answers will not be forthcoming until more labs agree to test for CWD forms. For this to happen, the benefits of doing tests for CWD forms as a means to save money in patient care must become apparent. The cost effectiveness of routinely using this type of laboratory test would most certainly benefit both patients and health insurers. Development of a test that can be used by commercial laboratories is the next step.
*As a side note: This process of reversion back to the classical form is a different process than normal bacterial replication, which is binary fission, which involves a cell wall separating the parent cell, thus creating a clone cell This process does not occur in the Lyme spirochete when creating an L-form. This means we really don’t understand the reproductive capabilities of this bacteria.