'New Hope' For Patients Suffering from Chronic Lyme Disease?

Every year science learns more and more about how bacteria affect the human body, but what do we really know about Borrelia Burgdorferi, the bacterium that causes Lyme and Lyme-like illness? 

A Little Background 

If you read the research of Dr's Burgdorfer, Barbour, Steere and others, you learn a great deal about Lyme. Believe me, there is no shortage of research on Borrelia Burgdorferi (B.b)--A quick Pubmed search reveals nearly 12,000 published research articles on Lyme Disease. However, with the advent of better DNA and Genetic testing scientists are now able to identify new keys to persistent infection. As science evolves, so must our approach to treating all diseases. I believe we are truly on the verge of a whole new discovery of Lyme Disease.

Dr. Kenneth Liegner says it best,

"It took medical science roughly 500 years to gain a good understanding of syphilis. We are but 40 years in to Lyme disease, caused by a spirochete considerably more genetically complex than Treponema pallidum, the organism causing syphilis.”

As I pointed out in an earlier post, there are 3 Basic Stages of Lyme Disease, and a 4th somewhat controversial stage or "syndrome" that occurs after antibiotic treatment. Stage 1-Primary Lyme (occurs days to weeks after infection); Stage 2-Secondary Lyme (occurs 3 weeks to 3 months after infection); Stage 3-Late Stage Lyme (occurs months to years later); Stage 4- Post Treatment Lyme Disease Syndrome aka PTLDS (Chronic symptoms that linger after a 2-4 week course of antibiotics).

The last stage, or syndrome, may be defined differently depending on which infectious disease theory you subscribe to. In the 'World of Lyme Research' there are basically two different theories:

1. Says that the continuation of symptoms that persist after treatment for a Lyme Disease infection are caused by damage to the immune system (or other yet to be defined bodily tissues); the other
2. Says that the chronicity of symptoms are a result of lingering persistent infection caused by Borrelia's ability to evade antibiotics and the immune system.

What Are Persister Cells?

The idea of bacterial persisters were first described by Joseph Bigger in 1944. In his 2007 Article, Dr. Kim Lewis of Northeastern University, reviews Persister Cells, Dormancy and Infectious Disease. Dr Lewis says, "Bigger discovered that penicillin lysed a growing population of staphylococcus ssp., but that a small number of persister cells, which were not simply antibiotic-resistant mutants, inevitably survived..." Bigger found that the E.Coli bacteria that survive after exposure to ampicillin form mutants that grew into persister cells. These persisters were able to survive at 1000 times the rate of non-mutants. Dr. Lewis suggests that dormant persister bacteria may play a much larger role in recalcitrant infectious diseases than previously thought. 

”About half of infectious diseases that are difficult to treat with antibiotics are not due to resistance but persisters” ~ Kim Lewis, 2012

Ed Yong does a fantastic job of describing persister cells in his 2012 New Scientist article entitled Sleeper Cells: "Our strongest antibiotics are being thwarted by bacteria that lie dormant, only to bounce back unharmed once the pressure is off."  In this article Yong interviews Dr. Kim Lewis:

      What is going on? It seems that this dormant state evolved to allow bacteria to cope with harsh environments, such as low oxygen levels, lack of nutrients or adverse temperatures. Today, it allows them to shrug off antibiotics. 

     Lewis describes them as the ultimate adversary. "Their function is to be not killed," he says. "They don't do anything else. They don't grow. They don't propagate. They don't do anything except survive." 

Image from "Sleeper Cells" by Ed Yong

Willy Knew What He Was Talking About

In 1999, Dr. Wilhelm "Willy' Burgdorfer (the scientist who discovered the bacteria that causes Lyme Disease) gave the Keynote Address at the 12th International Conference on Lyme Disease and other Spirochetal and Tick-borne Disorders. He reviewed the (then recent) publication by Brorson and Brorson on the "Conversion of Borrellia burgdorfer to Cystic Forms in Spinal Fluid"

Accordingly, B burgdorferi converted rapidly to cystic forms when transferred to spinal fluid. No normal spirochetes were left after 24 hours of incubation at 37° C; all were converted to cysts. When these cystic forms were transferred to a rich (BSK-H) medium, the cysts were converted back to normal, mobile spirochetes after incubation for 9 to 17 days.

These most recent findings do confirm the development of membrane-derived cysts, blebs, spherules, vesicles and the potential transformation to motile, helical spirochetes, not as part of a complex developmental cycle -- as postulated by Dutton and associates -- but rather as a "survival mechanism" of spirochetes to overcome or escape unfavorable conditions. 

Yes, you read that right. In 1999 Dr. Burgdorfer confirmed a process that had been newly discover about Lyme bacteria. When exposed to a foreign environment Borrelia would rapidly shape-shift to a dormant form allowing it to survive in the host. Burgdorfer goes on to say,

It is tempting to speculate, however, that the survival mechanism of spirochetes is responsible for the diverse pathology of these organisms as well as for their ability to survive as cystic forms thereby producing prolonged, chronic and periodically recurrent disease. 

Yes, you also read that right. In 1999, Dr. Burgdorfer revealed to the International Community his suspicion that these persistent forms of the Borrelia bacteria were capable of "prolonged, chronic and periodically recurrent disease."  Hmmm....🤔

Current and Ongoing Research

Now Jump forward to 2014. World renowned Johns Hopkins Tuberculosis and Cancer researcher Dr. Ying Zhang published Persisters, Persistent Infections and the Yin-Yang Model. It's a deep look into the more than 70 years of research of persister cells. He develops a "Yin-Yang" model that describes the ever changing persistent forms of fungi, parasites, viruses, and cancer cells that are involved in latent infections. Dr. Yang also clearly places Borrelia in the category of bacteria that are consistent with the phenomenon of developing persisters. It is a fantastic read for anyone who is interested in how bacteria form drug tolerance.

Norvect did a great interview with Dr. Zhang in September 2015 where he discusses the similarities between Tuberculosis and Lyme persister cells and the difference in treatment approaches to Early and Late Stage Lyme Disease. You can watch the short Video here.

Basically what you need to know is that antibiotics are designed to target different forms of bacteria--gram negative, gram positive, those with cell walls, and those without cell walls. Antibiotics can also be used to target bacterial proteins or interfere with the bacterial enzymes. Doxycycline for instance, is microbiostatic and relies on immune clearance of static bacteria in order to work.

Because B.b. evades the immune response, like a stealth bacteria, doxycycline alone may not be the most effective antibiotic for treating Lyme, especially in immunocompromised individuals. Most antibiotics are only able to kill bacteria during their active growing phase. Because B.b. can survive for many months in a dormant phase in places like deep tendons, connective tissue, joints and central nervous system without nutrients, many types antibiotics will be ineffective when used alone.

At any given point in time the Lyme bacteria will be present in multiple "pleomorphic" forms. Science has known that Treponema palladium, the bacteria that causes syphilis also has the ability to form atypical cystic forms allowing it to lay dormant for years before resurging to attack the nervous system. This is not a new discovery. Many bacteria do this, for example, Tuberculosis, Gonorrhea, and Mycobacteria like the one that causes Leprosy.

Pleomorphic forms of B.b. (a) spirochete, (b) bleb,  (c) round body,  (d) biofilm  (source) 

So what happens when you treat one of these bacteria with the wrong or too weak of an antibiotic? They can form resistance to the antibiotic and/or persistent forms of bacteria that will lay dormant until such time that the environment is favorable for them to grow again. Ying Zhang likens this to using a lawn mower for killing weeds.

There are multiple studies which have proven the Lyme Bacteria are capable of surviving in animals after a standard course of antibiotics. In fact, there is a preponderance of evidence from multiple labs, on multiple species using multiple drugs (doxycycline, amoxicillin, azithromycin, ceftriaxone, tigecycline) all with similar results of visible persistent infection in tissues after antibiotics. (UC Davis -Bartholdi, Hodzic et al.; Yale Univ- Bockenstedt et al; Univ Tuku- Yrjanainen et al; Cornel Univ- Straubinger et al; Tulane Univ- Embers et al.) 

For many years Dr. Lewis and Dr. Zhang have been devoting their time and energy to eradicating Borrelia persister cells in the laboratory. Well, this week Dr. Zhang published a highly anticipated study. In this he outlines two three-drug combination of antibiotics which he feels will be most effective against Lyme Persister cells, the form of Borrelia that many in the scientific community feel are contributing to Late Stage Lyme Disease (chronic form caused by delayed diagnosis) and PTLDS.

Can We Apply TB Science to Lyme Science?  

In his paper Dr. Zhang reveals Two triple drug combinations with highest activity against Borrelia burgdorferi Persisters: (link here) 

• Artemisinin/Cefoperazone/Doxycycline

• Sulfachlorpyridazine/Daptomycin/Doxycicline 

Note that both of these Drug combinations are from FDA approved libraries. The next step would be to apply these in animal models and human clinical trials to test the treatment theory outside of the laboratory.  Hopefully, it won't be long before we have more data.

We know from the Aucott studies that 10-20% of patients who are treated for early Lyme, and 40-60% of patients who are treated for late stage Lyme will be left with chronic symptoms. It wouldn't take a huge leap for most of us to believe that these chronic symptoms are caused by persistent infection, just as Dr. Willy Burgdorfer suggested to his audience on Friday, April 9, 1999.

As Dr. Zhang presented his findings on Saturday, May 14, 2016 at Massachusetts General Hospital during a conference on "Lyme Disease and Other Tick-borne Illnesses..." I can't help but wonder, was the Medical Community listening?