Lyme 101: The Three Forms of Borrelia + Corresponding Antibiotics

The 3 Forms of Borrelia burgdorferi, the causative bacterium of Lyme disease + the antibiotics commonly used to treat them

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Borrelia burgdorferi, the causative bacterium of Lyme disease, is able to transform into three distinct forms or morphs: spirochete, cell wall-deficient, and cystic. Research also indicates that Borrelia can form biofilms. These transformations permit bacterial survival and proliferation in the human body, and lead to the development of chronic Lyme disease.

Each form must be treated with different agents, which is why combination antimicrobial therapy is typically employed.

Spirochete Form

Shaped like a corkscrew, this is the “active” form. It is an anaerobic (can only tolerate low levels of oxygen) bacterium that has a cell wall and a flagellum (tail). Its shape and flagellum provide motility and allow it to burrow into tissue and organs. When it dies, its cell wall releases endoxins called lipopolysaccharides. (This might account for the Jarisch-Herxheimer or “herx” reaction some people experience during treatment.)

Tetracycline antibiotics are often used to combat this morph. Proper dosage and duration must be employed for tetracyclines to be bacteriCIDAL–to kill the Borrelia bacterium–verses bacterioSTATIC, which will only stop them from replicating. Doxycyline, minocycline, and tygecycline are examples of the most commonly prescribed tetracyclines.

Tetracyclines should be taken at least two hours apart from all of your supplements and dairy products, and you should not lie down for at least thirty minutes afterwards. While on tetracyclines, avoid sunlight as much as possible. Tetracyclines can cause severe sun sensitivity issues, even third degree and blistering burns.

Beta-lactam antibiotics are also often used. They include cephalosporins like cephtriaxone (intravenous or intramuscular), cefuroxime, and cefdinir, and penicillins like amoxicillin or intramuscular penicillin G benzathine. Beta-lactams work on the cell wall of the bacteria by inhibiting synthesis of the peptidoglycan layer. The peptidoglycan layer is a mesh-like structure made up of sugars and amino acids. Some cephalosporins can be rough on the liver. Make sure to get your liver and kidneys checked via regular blood tests such as a Complete Metabolic Panel at least every three months.

Cell Wall-Deficient Form

As the name implies, this form does not have a cellular wall. It is also referred to as the l-form or spheroplast.

Macrolides are used to treat this morph. The most common ones prescribed are azithromycin, clarithromycin, and roxithromycin. Macrolides work by binding irreversibly to the 50S subunit of bacterial ribosomes. Ribosomes are the protein factories of the cell, and by binding to the ribosome, macrolides inhibit translocation of tRNA during translation (the production of proteins under the direction of DNA).  They are bacteriostatic, meaning that they inhibit bacterial growth and reproduction. However, they can be bactericidal, meaning that they actually kill the bacteria, if your blood level concentration is high enough.

Some people can experience Q/T interval (cardiac) problems while on macrolides. Make sure you do not take more than your prescribed dose and take it at the same time everyday. Seek medical attention or call your doctor if you develop cardiac symptoms (new or worsening palpitations, tachycardia, rapid or varying pulse, pain, etc.). Macrolides can also induce ototoxicity in some people. If you start to have or notice an increase in your balance or hearing issues, or have pain in your ear, contact your physician immediately.

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Floroquinolones, such as levofloxacin and ciprofloxin, can also be used for this form, though they are most often used for Bartonella. Fluoroquinolones have a black box warning for tendinitis and neuropathy. In his book, The Lyme Disease Solution, Dr. Kenneth Singleton suggests implementing high doses of magnesium and vitamin C at least two weeks prior to going on and during any fluoroquinolone treatment to help avoid those side effects. If you notice any tendinitis whatsoever, especially in your Achilles tendon or calf muscle, contact your physician immediately.

Ketolides are also sometimes employed to treat the L-form. Telithromycin blocks protein synthesis by binding to domains II and V of 23S rRNA of the 50S ribosomal subunit. By binding at domain II, telithromycin retains activity against gram-positive cocci in the presence of resistance mediated by methylases (erm genes) that alter the domain V binding site of telithromycin. It may also inhibit the assembly of nascent ribosomal units. Ketek also comes with an FDA black box warning and should not be taken if you have myasthenia gravis. It can also tax the liver, so make sure to get regular metabolic blood tests done.

Cyst form 

The cystic form of Borrelia is dormant and immobile, and can remain totally hidden from the human immune system. It can survive antibiotics, starvation, pH changes, hydrogen peroxide, temperature variation, and most other adverse conditions.  It converts back to the spirochete form when conditions are favorable (for example, when antibiotics are not in use).

Anti-protozoals and anti-parasitics are used to treat the cyst form, most commonly metronidazole and tinidazole. These work by opening the cyst and converting it to one of the other forms above. Spirochete and l-form antibiotics then take over the job. Metronidazole and tinidazole can be rough on the liver so make sure to have your metabolic enzymes tested frequently. Metronidazole has been shown to cause cancer in laboratory animals. It is not known whether tinidazole increases the risk of developing cancer in humans, but since they have very similar molecular structures some professionals assume the same risks. Both metronidazole and tinidazole can cause neuropathy in the form of unusually severe headaches, numbness, and tingling in the extremities or other parts of the body, and other neurological issues. Sometimes it is hard to differentiate between side effects of medication or herxing, so be sure to notify your physician immediately if such symptoms begin or worsen while taking either of those prescriptions. Metronidazole and tinidazole should not be used during pregnancy; they are known to cause birth defects.


Dawn WilsonDawn Wilson is a former cellular biologist, and has held ecological planning and research positions with state agencies and universities. Her years of personal experience with Lyme and tick-borne diseases motivate her to encourage and support others through what can otherwise be an isolating and often misunderstood experience. Her goal is to build a network of people helping people. She is hopeful that greater awareness and outreach will bring about significant changes in current tick-borne disease doctrines and perceptions.

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  1. You mention the cyst form of borrelia can withstand temperature changes. I am sure it can to some degree, but I wanted to share my anecdotal experience. I had a tick bite and a persistent case of Lyme in 2012-2013. By accident, I learned that you can force the cyst form of borrelia into another form by sitting in an extremely hot bath. I used an indoor Jacuzzi tab that had a heating system to maintain temp, and while on antibiotics (a few weeks into treatment) I used this bath one night. Before entering the bath, I had enjoyed minimal symptoms of Lyme for a few days, but I assumed I had chased the bacteria into dormancy. When I got sufficiently heated, the bacteria “came alive” out of every single joint in my body, as well as my face and head. I had not a clue this would happen. They buzzed like angry bees, so much that I was vibrating in an extraordinary way. I stayed low under the water as far as I could. I noted that the buzzing emanated from the joints, but then tapered off the further the distance from each joint. I had the biggest die-off I ever experienced on the following day. Because I was on antibiotics, I believe the bacteria left cyst form due to the heat, hit the antibiotics in the bloodstream, and died. After I discovered this worked, I repeated it several more times, each time having a lesser die-off. In 2012-2013, I was under a doctor’s care for Lyme for about a year when I did these “hyperthermia” sessions. At this point in 2017 I am four years in remission.

  2. Interestingly, a rare subject matter among/of the Lyme Disease and Associated Infections and Mediated Diseases of Community. Kudos! Thank you! Please, disseminate w/ great earnest.
    “Lymie,” Greg Hawkins, SJ, Pharm.D., MS