Other useful links inc Under the Microscope & Lyme Biofilm
Updated 11th Jan 2016
Written text by Leena Meriläinen, and Leona Gilbert from Department of Biological and Environmental Sciences and NanoScience Center, University of Jyväskylä, Finland
Dr Alan MacDonald’s presentations on spiros, blebs, granules & cystic forms:
Part I: Spirochetes are Expected to present as spiral or corkscrew shaped profiles. This idea comes from Textbook depictions. Spiral profiles are in fact, only ONE form of many other alternate PERFECT spirochetal Forms ; These Include Round body Spirochetes [Cystic spirochetes], Granular dot like Spirochetes, Biofilm Community Spirochetes, and Liposomal {bleb -like] Spirochetes.
Part II: Cystic Borrelia are under appreciated in borrelia biology. This Lecture discusses the formation of Cystic Borrelia, and the Pathological effects in the human body which are associated with Cystic borrelia, especially in the Brain.
Examining Lyme Spirochete’s Bag of Immune-Evasive Tricks by Keith Berndtson, MD – this article explains why borrelia bacteria can be difficult to test, treat & be noticed by the immune system, includes shape shifting, antigen variants (outer surface proteins) & more.
Effects of penicillin, ceftriaxone, and doxycycline on morphology of Borrelia burgdorferi.
Antimicrob Agents Chemother. 1995 May; 39(5): 1127–1133.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC162695/
(full paper available in link)
Lyme Disease Causing Spirochetes As Shape Shifters: Implications For Treatment
blog post by Dannielle…
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Updated 2nd Oct 2012
Lyme Disease Studies on the Cystic Form of Borrelia burgdorferi Mechanisms of Persistence
http://www.docstoc.com/docs/4484812/Lyme-Disease-Studies-on-the-Cystic-Form-of-Borrelia
Lots of useful info about spirochetal cyst forms:
http://www.lymeinfo.net/medical/LDCysts.pdf
http://www.lymeinfo.net/medical/LDBibliography.pdf
Some more studies from Brorson on cyst formations:
http://kroun.ulmarweb.dk/York2003/Brorson.htm
Formation of dormant borrelia stages (PDF)
http://www.emc2012.org.uk//documents/Abstracts/Abstracts/EMC2012_0697.pdf
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Updated 2nd Aug 2012
Borrelia survive by shape-shifting
http://www.thefreelibrary.com/Borrelia+survive+by+shape-shifting.-a0202661727
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Updated 2nd Aug 2012
A life cycle for Borrelia spirochetes?
Alan B. MacDonald
Several cystic varieties exist. The first of these is the “inducible” cystic Borrelia, which is easily produced by placing the corkscrew forms into a “hostile environment” such as liquid media containing antibiotics, or acid pH, or starvation conditions. Under these circumstances, the corkscrews “round up” and are internalized. This “encystment” is a rapid event. The shortest elapsed time in video microscopy for encystment to begin is less than 1 min, but longer encystments have been noted experimentally. Like a marsupial in a pouch, the corkscrew is “infolded” into its own surface membrane. Darkfield microscopy and electron microscopy studies demonstrate within this variety of cystic Borrelia, that the “parent” form is still visible, and that the corkscrew form is capable of rapidly re-emerging from its “cocoon” if the adverse external environment is corrected.
A second sphere in the Borrelia life cycle is the granule. Granular spirochetal forms were known to Noguchi and his contemporaries [11]. Granular derivatives emerge from “senescent” spirochetes, by a process of “segmentation” of the inner DNA containing regions of the axial cylinder. The granular elements contain either DNA or RNA, derived from the “parent” and incrementally evolve from a “Morse Code” dot and dash profile within the cylinder. When released from the confines of the inner intact spirochetal cylinder, these granules are able to “round up” in liquid media. ..
..Dr. Gabriel Steiner [12] correctly implicated granular spirochetal profiles as agents of tissue injury in his landmark studies of human autopsy tissues from Multiple Sclerosis. In Alzheimer’s disease the granules within diseased and dying nerve cells of the hippocampus may be internalized Borrelia spirochetal granular forms, based on DNA in situ hybridization data.
The third sphere consists of L forms of spirochetes. L forms describe any bacterium which has lost its cell wall, but which has not lost its bacterial viability in the process. Spirochetal L forms are just as reasonable and equally contentious as cell wall deficient forms of any other microbe. If the Lister Institute conceptual model is embraced, then morphologic plasticity of Borrelia L forms is not a political “hot button”. Cell wall deficient microbes share with the “snowflake” the constraints that are implicit with any “soap bubble”, namely an ephemeral existence. Horizontal DNA transfer from Borrelia to other prokaryote or to eukaryotic cells might be mediated by L forms.
Additional special types of spirochetal morphology are addressed in the last two “bullets”, namely liberated periplasmic flagellae (undocked from their parent corkscrew forms) and finally, genetic mutants of spirochetes which do not demonstrate the corkscrew profile.
http://www.theoneclickgroup.co.uk/documents/Borreliosis/A%20life%20cycle%20for%20Borrelia%20spirochetes.htm
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Updated 5th Jul 2012
A fascinating looks at cysts, spiros, granules & blebs
12th International Conference on Lyme Disease and Other Spirochetal and Tick-Borne Disorders
Day 1 – April 9, 1999
Keynote Address – The Complexity of Vector-borne Spirochetes (Borrelia spp) by Willy Burgdorfer discoverer of Lyme spirochete Borrelia Burdgdorferi
http://www.lymenet.de/literatur/12tbdconference/day1/day1.htm#The Complexity of Vector-borne Spirochetes
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Structures of Lyme Bacteria
The Complexities of Lyme Disease
A Microbiology Tutorial
by Thomas M. Grier M.Sc.
The structure of the Lyme spirochete is unlike any other bacteria that has ever been studied before. It is one of the largest of the spirochetes (0.25 microns x 50 microns) It is as long, as a fine human hair is thick. Borrelia burgdorferi is a highly motile bacteria, it can swim extremely efficiently through both blood and tissue because of internal propulsion. It is propelled by an internal arrangement of flagella, bundled together, that runs the length of the bacteria from tip to tip. Like other Borrelia bacteria Borrelia burgdorferi has a three layer cell wall which helps determine the spiral shape of the bacteria. What makes this bacteria different from other species, is that it also has a clear gel-like coat of glyco-proteins which surround the bacteria. This extra layer is sometimes called the Slime Layer or S-layer. (See diagram 1) (45,46,59)
This means: This extra layer of glyco-proteins may act like a stealthy coat of armor that protects and hides the bacteria from the immune system. The human immune system uses proteins that are on the surface of the bacteria as markers, and sends attacking antibodies and killer T-cells to those markers, called outer surface protein antigens (OSP antigens). This nearly invisible layer is rarely seen in washed cultures, but can be seen regularly in tissue biopsies.(46)
The Lyme bacteria is different from other bacteria in its arrangement of DNA. Most bacteria have distinct chromosomes that are found floating around inside the cytoplasm. When the bacteria starts to divide and split in two, the chromosomes divide and the new copies of the chromosomes enter the new cell. The arrangement of DNA within Borrelia burgdorferi is radically different. It is arranged along the inside of the inner membrane. It looks something like a net embedded just underneath the skin of the bacteria. (46)
This means: We really don’t understand the mechanisms of how Bb regulates its genetic material during its division.
Another unique feature to Borrelia burgdorferi are Blebs. This bacteria replicates specific genes, and inserts them into its own cell wall, and then pinches off that part of its cell membrane, and sends the bleb into the host. Why it does this we don’t know. But we do know that these blebs can irritate our immune system. Dr. Claude Garon of Rocky Mountain Laboratories has shown that there is a precise mechanism that regulates the ratio of the different types of blebs that are shed. (46) In other bacteria the appearance of blebs often means the bacteria can share genetic information between themselves. We don’t know if this is possible with Borrelia species. There have been reports of a granular form of Borrelia, which can grow to full size spirochetes, and reproduce. These granules are so small that they can be filtered and separated from live adult spirochetes by means of a micro-pore filter. (Stealth Pathogens Lida Mattman Ph.D. 66)
The division time of Borrelia burgdorferi is very long. Most other pathogens such as Streptococcus, or Staphylococcus, only take 20 minutes to double, the doubling time of Borrelia burgdorferi is usually estimated to be 12-24 hours. Since most antibiotics are cell wall agent inhibitors, they can only kill bacteria when the bacteria begins to divide and form new cell wall.(35,59-62)
This means: Since most antibiotics can only kill bacteria when they are dividing, a slow doubling time means less lethal exposure to antibiotics. Most bacteria are killed in 10-14 days of antibiotic. To get the same amount of lethal exposure during new cell wall formation of a Lyme spirochete, the antibiotic would have to be present 24 hours a day for 1 year and six months! Note: Antibiotics kill bacteria by binding to the bacteria’s ribosomes, and interrupting the formation of cell wall proteins.
Like other spirochetes, such as those that cause Syphilis, the Lyme spirochete can remain in the human body for years in a non-metabolic state. It is essentially in suspended animation, and since it does not metabolize in this state, antibiotics are not absorbed or effective. When the conditions are right, those bacteria that survive, can seed back into the blood stream and initiate a relapse. (59-62,70)
This means: Just because a person is symptom free for long lengths of time doesn’t mean they aren’t infected. It may be a matter of time. Whereas viral infections often impart a lifelong immunity, Lyme, like other bacterial infections, does not retain active immunity for long periods of time. People are often reinfected with Lyme. (96)
How does the Lyme bacteria travel from the bloodstream to other tissues? While we have known for a long time that the Lyme spirochete can show up in the brain, eyes, joints, skin, spleen, liver, GI tract, bladder, and other organs, we didn’t understand the mechanism by which it could travel through capillaries and cell membranes. (Abstract 644) Then Dr. Mark Klempner presented at the 1996 LDF International Lyme Conference an interesting paper that gave us part of the answer.
Many researchers have observed that the Lyme spirochete attaches to the human cells’ tip first. It then wiggles and squirms until it enters the cell. What Dr. Klempner showed was that when the spirochete attached to the human host cell, it caused that cell to release digestive enzymes that would dissolve the cell, and allow the spirochete to go wherever it pleases. This is very economical to the bacteria to use our own cell’s enzymes against us, because it does not need to carry the genes and enzymes around when it travels. Dr. Klempner also showed that the spirochete could enter cells such as the human fibroblast cell (The skin cell that makes scar tissue.) and hide. Here the pathogen was protected from the immune system, and could thrive without assault. More importantly, when these Bb-fibroblast cultures were incubated with 10 x the MIC for IV Rocephin, two thirds of the cultures still yielded live spirochetes after two weeks, and in later experiments for more than 30 days. If we can’t kill it in a test tube at these high concentrations in four weeks, how can we hope to kill it in the human body? (22,48,79,80,)
This means: The infection can enter the tissue that is optimal for its survival, and it may evade the immune system and antibiotics by hiding inside certain types of cells.
Another interesting observation about this bacteria is how it interacts with our body’s immune system; Dr. David Dorward of Rocky Mountain Labs made a video tape of how Borrelia burgdorferi acts when surrounded by B-cells. (The type of white blood cell that makes antibody.) The spirochete attached tip first, entered the B lymphocyte, multiplied and ruptured the cell. It repeated this process for three days until the B-cells were able to come to an equilibrium. A matter of concern was that some of the spirochetes were able to strip away part of the B-cell’s membrane, and wear it like a cloak. (Dorward, Hulinska 1994 LDF Conference Vancouver BC)
This means: If this spirochete is evolved enough to attack our B-lymphocytes, then it may also be evolved in other ways that we do not yet understand. It is for certain that its ability to kill B-lymphocytes evolved as part of a defense mechanism to evade its own destruction. The observation that it can use the B-cell’s own membrane as camouflage indicates that it may be able to go undetected by our immune system. The way our immune system is supposed to work is that it recognizes foreign invaders as being different from self, and attacks the infection.
Unfortunately, the immune system sometimes attacks our own cells. This is called autoimmune disease. If a foreign invader has a chemical structure similar to our own tissue antigens, our bodies sometimes make antibodies against our own tissues. In people with Lyme disease scientists have discovered auto-antibodies against our own tissues including nerve cells (axons), cardiolipid, myelin (also seen in MS), myelin basic protein (also seen in MS), and neurons (brain cells) (23,28,38-40,43,45,56,57,60,88)
When the immune system finds a foreign invader, it tags that invader in a number of ways. A cell called the macrophage can engulf the bacteria, and then communicate to other immune cells the exact description of the bacteria. Another cell might mark the cell with antibody which attracts killer T-cells. Some types of T-cells communicate to other cells what to attack, and regulate the immune assault. But sometimes the body can produce a type of antibody that doesn’t attack or help. A blocking antibody will attach and coat the intruder, but it won’t fix compliment, and it shields the bacteria from further immune recognition. In Lyme we have seen quantities of IgG4 blocking antibody such as is seen in some parasitic infections. (Tom Schwann RML 92 LDF Conference) *Note: Compliment is a term used for a series of 18 + digestive proteins that are only activated by signals from our immune system, such as compliment fixing antibodies.
In order for the immune system to make an attacking antibody, the immune system must first find an antigen which it can attack. Unfortunately, as seen by freeze fracture electron microscope, photographs of the Lyme bacteria show that most of the antigens are on the inside of the inner membrane, and not on the outside. (60) This makes the bacteria less visible to the immune system and more difficult to attack. The most intriguing fact about Borrelia spirochetes is their well documented ability to change the shape of their surface antigens when they are attacked by the human immune system. When this occurs, it takes several weeks for the immune system to produce new antibodies. During this time the infection continues to divide and hide. (1,47,63,66)
It appears that Borrelia are able to change their surface antigens many times, and can do it quickly. In one study by Dr. Andrew Pachner MD, he infected mice with a single strain of Borrelia burgdorferi. After several weeks, he was able to isolate two slightly different forms of the bacteria. The bacteria from the bloodstream was attacked and killed by the mouse’s immune sera, but the bacteria isolated from the mouse’s brain was unaffected by the immune sera. The bacteria isolated from the mouse’s brain had a new set of surface antigens. It appears that contact with the CNS caused the bacteria to change its appearance. Since the brain is isolated from the immune system and is an immune privileged site, the bacteria became its own separate strain. (47,97)
This means: Infections of the bloodstream may be different from the infections that are sequestered in the brain. While we continue to have active immunity in the bloodstream, the brain has no immune defenses except for circulating antibodies. So, if those circulating antibodies are ineffective to attack the bacteria in the brain, then the brain is left without any defenses, and the infection goes unabated.
Over 100 references, abstracts and diagrams are inserted into the text to support the statements in this chapter.
Another peculiar observation of these bacteria is seen inside the bacteria. When the genetic control mechanisms of this bacteria are inhibited with antibiotics known as DNA Gyrase Inhibitors (ciprofloxin) the bacteria start to produce bacterio-phage. A phage is a virus that specifically attacks bacteria. In this case there are two distinct forms. This means the Lyme bacteria at one time were attacked by viruses. It was able to suppress them, but the DNA to make the phage is still incorporated within the DNA of the bacteria. Perhaps activation of this phage could one day be beneficial to treating chronic Lyme patients? (JTBD 94)
What happens when the infection gets to the brain? In the case of Lyme disease, every animal model to date shows that the Lyme spirochete can go from the site of the bite to the brain in just a few days. (41,60, abstract 644) While we know these bacteria can break down individual cell membranes and capillaries, its entrance into the brain is too pronounced for such a localized effect. When the Lyme bacteria enters the human body, we react by producing several immune regulatory substances known as cytokines and lymphokines. Several of these act in concert to break down the blood brain barrier. (E.g. Il-6, Tumor Necrosis Factor-alpha, Il-1, Transforming Growth Factor-beta etc.) In addition to affecting the blood brain barrier, these cytokines can make us feel ill, and give us fevers. (54,60,) (JID 1996:173, Jan)
Since the brain has no immune system, it prevents infection by limiting what can enter the brain. The capillary bed that surrounds the brain is so tight that not even white blood cells are allowed to enter. Many drugs can’t enter either, making treatment of the brain especially hard. For the first ten days of a Lyme infection, the blood brain barrier is virtually nonexistent. This not only allows the Lyme bacteria to get in, but also immune cells that can cause inflammation of the brain. (41) *Note: The breakdown of Bb was shown to occur by tagging WBCs, albumin, and other substances known not to cross the BBB with radioactive Iodine. The CSF was tested, and then the animals were infected with Bb. Then the CSF was tested everyday for several weeks. The result: No cross over of Iodine in the control group, 100% crossover in the infected group for 10 days. The infection had the same result as injecting the radioactive iodine directly into the brain. (60)
When the human brain becomes inflamed, cells called macrophages respond by releasing a neuro-toxin called quinolinic acid. This toxin is also elevated in Parkinson’s Disease, MS, ALS, and is responsible for the dementia that occurs in AIDS patients. What quinolinic acid does is stimulate neurons to repeatedly depolarize. This eventually causes the neurons to demyelinate and die. People with elevated quinolinic acid have short-term memory problems. (27,29-37,40-42,74,75, 82-84,87-90)
This means: If we think of all of our brain cells like telephone lines, we can visualize the problem. If all of the lines coming in are busy, we can’t learn anything. If all of the lines going out are busy, we can’t recall any memories. Our thinking process becomes impaired.
A second impairment to clear thinking that Lymies experience is the restriction of proper circulation within the blood vessels inside the brain. Using an instrument called the Single Photon Emission Computer Tomography scanner (SPECT scans), we are able to visualize the blood flow throughout the human brain in 3-D detail. What was seen in the brains of chronic neurological Lyme patients was an abnormal “swiss-cheese” pattern of blood flow. The cortical, or thinking region of the brain, was being deprived of good circulation; the occipital (eyesight) regions had an increase flow. This could help explain why most Lyme patients complain of poor concentration and overly sensitive eyes. (91)
http://www.lymeneteurope.org/info/the-complexities-of-lyme-disease
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Characteristics of Borrelia burgdorferi
• Over 1500 gene sequences
• At least 132 functioning genes (in contrast T Pallidium has 22 functioning genes)
• 21 plasmids (three times more than any known bacteria
• “Stealth” pathology: evades the immune response
Borrelia has over 1500 gene sequences so this is a very, very complex bacteria. Now, unfortunately, we really don’t know what over 1400 of those genes do or if they do anything but when you talk about not having the gene for something in this bacteria, the answer is, well you don’t really know that, I mean, the gene might be there, we just haven’t found it yet. However, we do know that there are at least 132 functioning genes in Borrelia and this is in contrast to Treponema pallidum which is the spirochaete that causes Syphilis. This bacteria has only 22 functioning genes so Borrelia is a much more complex organism from a genetic point of view compared to the organism that causes Syphilis.
Now, in addition, to all of these functioning genes, the structure of Borrelia is quite interesting because it has 21 plasmids and plasmids are these extra chromasomal strands of DNA that are kind of the early response mechanism for bacteria.
So if a bacterium wants to do something very quickly, if it has a plasmid, the plasmid can make a protein very quickly to do things like avoid the immune system or enter cells or do whatever the bacteria needs to do to survive. 21 plasmids is three times more than any other known bacteria. I think that Chlamydia has the next greatest number – that’s 7. So this is an organism that has a very, very adaptable and effective gene structure in terms of infecting people.
In addition, Borrelia qualifies as an organism that has true stealth pathology and what is meant by that is that the bacteria can evade the immune system by making different types of proteins that do things such as complement the immune response or get into cells with different types of cell receptors and this stealth pathology is one reason why Borrelia can persist in humans and cause the type of chronic problems that we see. I should also mention that a lot of this work comes from the Lab of Sherwick Casjens who is at the University of Utah and also Tom Schwan at his Lab at the Rocky Mountain Labs in Montana. Dr Casjens has been working on this for a number of years and if you want to look at the complexity of the genetics of Borrelia you should look at his work and it has been extensively published even though very few people pay attention to it.
by Dr Ray Stricker – York 2004 LDA Conference
http://www.lymediseaseaction.org.uk/conference/t_2004_3_p.htm NB link now broken!
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(From a poster called Knotweed: 8th Sept, 2010)(he gave full permission to pass this along)
Bb prophage, in short:
All Bb strains that cause Lyme disease (Bb sensu lato) or relapse fever (some
other Bb strains) have a so called prophage called phi-BB1, located on the cp32
plasmid. The prophage is a gene, part of the Borrelia DNA, that can get
activated in very specific conditions. When activated it is a recipe to make
phages, a bacterial virus that will kill the Borrelia from inside.
phiBB1 gets activated by adverse conditions, e.g. when the bacterial DNA is
damaged by chemicals like flagyl or tinidazole. Flagyl is even used in the lab
to produce the prophage, it is a very reliable ‘cue’.
This virus kills the Borrelia by making holes in its outer layers. It then
spreads inside the host, where it probably will find and kill other Borrelia.
The phiBB1 phage also exist in very small numbers in Bb cultures; scientists are
not sure what its function is. It may help to ‘revatalize’ old Bb cultures by
killing off most of the bacteria and stimulating them to regrow.
So, it almost seems as if Bb has some built-in ‘self-destruct button’. Maybe we
can use that to get rid of it. On the other side, the phage might be dangerous
because there is evidence for transfer of Borrelia DNA to humans (research from
Alan McDonald with Alzheimer patients). We don’t know what mechanism is causing
that, but the prophage is a likely cause (similar to retroviruses) .
So, activating the prophage kills the Borrelia, but may cause DNA damage in the
host. I wouldn’t be surprised if this is related to the ‘Gates of Hell’
experience that many people know from taking high doses of Flagyl.
Borrelia also has a second resident phage, but very little is known about that
at this time.
refs: Skotarczak B. Adaptation factors of Borrelia for host and vector. Ann Agric Environ Med. 2009
Jun;16(1):1-8. PMID: 19572471.
references for the prophage part below:
59-65 is about bacteriophages and prophages in general
66,67,70 is about the Borrelia prophage
68,69 is about effects of metronidazole (flagyl) and similar drugs
71-76 is about general medical aspects of prophages and viruses
59: Skotarczak B. Adaptation factors of Borrelia for host and vector. Ann Agric
Environ Med. 2009 Jun;16(1):1-8. PMID: 19572471.
60: Duckworth DH, Gulig PA. Bacteriophages: potential treatment for bacterial
infections. BioDrugs. 2002;16(1):57-62. PMID: 11909002.
61: Hanlon GW. Bacteriophages: an appraisal of their role in the treatment of
bacterial infections. Int J Antimicrob Agents. 2007 Aug;30(2):118-28. Jun 12. PMID: 17566713.
62: Parisien A, Allain B, Zhang J, Mandeville R, Lan CQ. Novel alternatives to antibiotics: bacteriophages, bacterial cell wall hydrolases, and antimicrobial peptides. J Appl Microbiol. 2008 Jan;104(1):1-13. PMID: 18171378.
63: Miller JC, Stevenson B. Borrelia burgdorferi erp genes are expressed at
different levels within tissues of chronically infected mammalian hosts. Int J Med Microbiol. 2006 May;296 Suppl 40:185-94. PMID: 16530008.
64: Casjens S. Prophages and bacterial genomics: what have we learned so far?
Mol Microbiol. 2003 Jul;49(2):277-300. PMID: 12886937.
65: Brüssow H, Canchaya C, Hardt WD. Phages and the evolution of bacterial
pathogens: from genomic rearrangements to lysogenic conversion. Microbiol Mol Biol Rev. 2004 Sep;68(3):560-602. PMID: 15353570.
66: Eggers CH, Samuels DS. Molecular evidence for a new bacteriophage of
Borrelia burgdorferi. J Bacteriol. 1999 Dec;181(23):7308-13. PMID: 10572135.
67: Zhang H, Marconi RT. Demonstration of cotranscription and 1-methyl-3-nitroso-nitroguanidine induction of a 30-gene operon of Borrelia burgdorferi: evidence that the 32-kilobase circular plasmids are prophages. J Bacteriol. 2005 Dec;187(23):7985-95. PMID: 16291672.
68: Edwards DI. Mechanisms of selective toxicity of metronidazole and other
nitroimidazole drugs. Br J Vener Dis. 1980 Oct;56(5):285-90. PMID: 7000306
69: Stanton TB, Humphrey SB, Sharma VK, Zuerner RL. Collateral effects of
antibiotics: carbadox and metronidazole induce VSH-1 and facilitate gene transfer among Brachyspira hyodysenteriae strains. Appl Environ Microbiol. 2008 May;74(10):2950-6. PMID: 18359835.
70: Eggers CH, Kimmel BJ, Bono JL, Elias AF, Rosa P, Samuels DS. Transduction by
phiBB-1, a bacteriophage of Borrelia burgdorferi. J Bacteriol. 2001 Aug;183(16):4771-8. PMID: 11466280.
71: Wang X, Kim Y, Wood TK. Control and benefits of CP4-57 prophage excision in
Escherichia coli biofilms. ISME J. 2009 Oct;3(10):1164-79. PMID: 19458652.
72: García-Contreras R, Zhang XS, Kim Y, Wood TK. Protein translation and cell
death: the role of rare tRNAs in biofilm formation and in activating dormant phage killer genes. PLoS One. 2008 Jun 11;3(6):e2394. PMID: 18545668.
73: Lu TK, Collins JJ. Engineered bacteriophage targeting gene networks as
adjuvants for antibiotic therapy. Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4629-34. PMID: 19255432.
74: MacDonald AB. Transfection “Junk” DNA – a link to the pathogenesis of
Alzheimer’s disease? Med Hypotheses. 2006;66(6):1140-1. PMID: 16481123.
75: Fritzsche M. Geographical and seasonal correlation of multiple sclerosis to
sporadic schizophrenia. Int J Health Geogr. 2002 Dec 20;1(1):5. PMID: 12537588.
76: Ryan F. I, virus: Why you’re only half human. NewScientist, 27 January 2010.
For anyone interested Niek has an article published a few years ago re: Lyme
testing. It’s in Dutch but google translate can help – the cartoons are really
funny!!!
http://www.lymevereniging.nl/file.php?id=178
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Transformation of cystic forms of Borrelia burgdorferi to normal, mobile spirochetes.
Infection 1997 Jul-Aug;25(4):240-6
Brorson O, Brorson SH
Dept. of Microbiology, Ulleval University Hospital, Oslo, Norway.
The purpose of this study was to evaluate the behaviour of Borrelia burgdorferi under controlled conditions. The occurrence of cystic forms of Borrelia burgdorferi in vitro was noted, and these cysts were able to be transformed to normal, mobile spirochetes. B. burgdorferi was cultivated in a commercial culture medium without serum. The spirochetes multiplied only slowly in this medium, and transformation to encysted forms was observed after 1 week. When these cysts were transferred to the same culture medium with rabbit serum, the encysted forms developed into regular, mobile spirochetes after 6 weeks, and their regeneration time was normal. Examination of these cysts in the transmission electron microscope revealed transverse fission inside the cysts. It is probable that similar phenomena may occur in vivo under conditions unfavourable for spirochetes. These observations may help to explain why diagnosis and treatment of B. burgdorferi infections in humans can be difficult.
PMID: 9266264, UI: 97411286
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Metamorphosis of Borrelia burgdorferi organisms – RNA, lipid and protein composition in context with the spirochetes’ shape
Journal of Basic Microbiology 21 OCT 2010
1. Samiya Al-Robaiy1,2,†,
2. Hassan Dihazi3,†,
3. Johannes Kacza4,
4. Johannes Seeger4,
5. Jürgen Schiller5,
6. Daniel Huster5,
7. Jens Knauer1,6,
8. Prof. Dr. Reinhard K. Straubinger1,7,*
Article first published online: 21 OCT 2010
DOI: 10.1002/jobm.201000074
http://onlinelibrary.wiley.com/doi/10.1002/jobm.201000074/abstract
Abstract
Borrelia burgdorferi, the agent of Lyme borreliosis, has the ability to undergo morphological transformation from a motile spirochetal to non-motile spherical shape when it encounters unfavorable conditions. However, little information is available on the mechanism that enables the bacterium to change its shape and whether major components of the cells – nucleic acids, proteins, lipids – are possibly modified during the process. Deducing from investigations utilizing electron microscopy, it seems that shape alteration begins with membrane budding followed by folding of the protoplasmatic cylinder inside the outer surface membrane. Scanning electron microscopy confirmed that a deficiency in producing functioning periplasmic flagella did not hinder sphere formation. Further, it was shown that the spirochetes’ and spheres’ lipid compositions were indistinguishable. Neither phosphatidylcholine nor phosphatidylglycerol were altered by the structural transformation. In addition, no changes in differential protein expression were detected during this process. However, minimal degradation of RNA and a reduced antigen-antibody binding activity were observed with advanced age of the spheres. The results of our comparisons and the failure to generate mutants lacking the ability to convert to spheres suggest that the metamorphosis of B. burgdorferi results in a conditional reconstruction of the outer membrane. The spheres, which appear to be more resistant to unfavorable conditions and exhibit reduced immune reactivity when compared to spirochetes, might allow the B. burgdorferi to escape complete clearance and possibly ensure long-term survival in the host. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
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Persisting atypical and cystic forms of Borrelia burgdorferi and local inflammation in Lyme neuroborreliosis
Judith Miklossy*1, Sandor Kasas2, Anne D Zurn3, Sherman McCall4,
Sheng Yu1 and Patrick L McGeer1
Background: The long latent stage seen in syphilis, followed by chronic central nervous system infection and inflammation, can be explained by the persistence of atypical cystic and granular forms of Treponema pallidum. We investigated whether a similar situation may occur in Lyme neuroborreliosis.
Conclusion: The results indicate that atypical extra- and intracellular pleomorphic and cystic forms of Borrelia burgdorferi and local neuroinflammation occur in the brain in chronic Lyme neuroborreliosis. The persistence of these more resistant spirochete forms, and their intracellular location in neurons and glial cells, may explain the long latent stage and persistence of Borrelia infection. The results also suggest that Borrelia burgdorferi may induce cellular dysfunction and apoptosis. The detection and recognition of atypical, cystic and granular forms in infected tissues is essential for the diagnosis and the treatment as they can occur in the absence of the typical spiral Borrelia form.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2564911/pdf/1742-2094-5-40.pdf
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Formation and cultivation of Borrelia burgdorferi spheroplast-L-form variants.
Infection 1996 May-Jun;24(3):218-26
Mursic VP, Wanner G, Reinhardt S, Wilske B, Busch U, Marget W
Max von Pettenkofer-Institut, Ludwig-Maximilians-Universitat München, Germany.
As clinical persistence of Borrelia burgdorferi in patients with active Lyme borreliosis occurs despite obviously adequate antibiotic therapy, in vitro investigations of morphological variants and atypical forms of B. burgdorferi were undertaken. In an attempt to learn more about the variation of B. burgdorferi and the role of atypical forms in Lyme borreliosis, borreliae isolated from antibiotically treated and untreated patients with the clinical diagnosis of definite and probable Lyme borreliosis and from patient specimens contaminated with bacteria were investigated. Furthermore, the degeneration of the isolates during exposure to penicillin G in vitro was analysed. Morphological analysis by darkfield microscopy and scanning electron microscopy revealed diverse alterations. Persisters isolated from a great number of patients (60-80%) after treatment with antibiotics had an atypical form. The morphological alterations in culture with penicillin G developed gradually and increased with duration of incubation. Pleomorphism, the presence of elongated forms and spherical structures, the inability of cells to replicate, the long period of adaptation to growth in MKP-medium and the mycoplasma-like colonies after growth in solid medium (PMR agar) suggest that B. burgdorferi produce spheroplast-L-form variants. With regard to the polyphasic course of Lyme borreliosis, these forms without cell walls can be a possible reason why Borrelia survive in the organism for a long time (probably with all beta-lactam antibiotics) [corrected] and the cell-wall-dependent antibody titers disappear and emerge after reversion. Published erratum appears in Infection 1996 Jul-Aug;24(4):335
http://www.ncbi.nlm.nih.gov/pubmed?term=8811359
PMID: 8811359, UI: 96407306
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Did You Know?
About the spirochete:
The spirochete is as long, as a fine human hair is thick. Borrelia burgdorferi is a highly mobile bacteria, it can swim extremely efficiently through both blood and tissue because of internal propulsion. It is propelled by an internal arrangement of flagella, bundled together, that runs the length of the bacteria from tip to tip.
Many researchers have observed that the Lyme spirochete attaches to the human cells’ tip first. It then wiggles and squirms until it enters the cell. What Dr. Klempner showed was that when the spirochete attached to the human host cell, it caused that cell to release digestive enzymes that would dissolve the cell, and allow the spirochete to go wherever it pleases.
http://www.lymeneteurope.org/info/the-complexities-of-lyme-disease
Granules or blebs:
Lyme spirochetes have also been seen shuddering violently or breaking into pieces, producing small particles called granules or blebs. Radolf and Bourell (1994) believe that the granules are “pinched-off” bits of cell wall which have been shown to contain DNA material (Brorson and Brorson 1997). Filgueira and others (2000) argue that granules are the remnants of previous outer surface proteins which have been shed in an attempt to confuse and evade the immune system, as described above (cf. Coyle and others 1995). Others have observed the formation of blebs in response to the presence of a strong immune response or powerful antibiotics, suggesting that granule formation is another way that Bb survives the action of bactericidal agents (Sadziene and others 1994, Dever and others 1993).
http://www.natcaplyme.org/index.php?module=Pagesetter&func=viewpub&tid=9&pid=2
L-Forms:
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.
http://www.lymeneteurope.org/info/notes-and-observations-on-cell-wall-deficient-forms
Cyst Forms:
The cyst form of B. burgdorferi develops when a single Lyme spirochete curls into a ball and forms a cocoon around itself, which is impermeable to most antibiotics.
Cyst formation in Bb occurs in response to common antibiotics such as ceftriaxone and penicillin (Murgia and others 2002, Kersten and others 1995). Researchers have also induced cyst formation by exposing the Lyme disease spirochete to other stressors, such as nutrient deprivation (Brorson and Brorson 1998b; Brorson and Brorson 1997) or high temperature, extreme pH variations, and the presence of hydrogen peroxide (Murgia and Cinco 2004). Gruntar and others (2002) found that B. garinii cysts proved infective when introduced into mice and could even survive freeze-thawing. Another study suggested that Lyme spirochetes prefer the cystic form when exposed to cerebro-spinal fluid, a possible reason why spinal taps often produce a low yield in diagnostic testing for Lyme disease (Brorson and Brorson 1998a).
http://www.natcaplyme.org/index.php?module=Pagesetter&func=viewpub&tid=9&pid=2
Biofilms:
Emerging research indicates that biofilm may be a significant factor in Lyme disease and subsequently will impact requirements for treatment. Biofilm is a polysaccharide matrix that traps the bacteria making it harder for antibiotics to reach and destroy them.
Biofilm protocols have five main goals:
1. Eat through the goo-like matrix using enzymes and thinning agents
2. Break the bonds between the goo using Ca-EDTA
3. Kill the now-exposed bugs using antimicrobials
4. Sweep the whole mess out using fibers and binders
5. Rebuild the gut lining with happy, healthy critters
http://www.lymebook.com/biofilm – an interesting book about the role of biofilm and source of biofilm protocols.
Click here for a must see video showing cysts, spirochetes & granular forms in one massive bio-film mass! http://www.youtube.com/watch?v=a4uNDWdChM8&feature=related
Did you know that the spirochete can move faster than any human cell in the body?
In order to clear the body of infecting spirochetes, phagocytic cells must be able to get hold of them. In real-time phase-contrast videomicroscopy we were able to measure the speed of Borrelia burgdorferi (Bb), the Lyme spirochete, moving back and forth across a platelet to which it was tethered. Its mean crossing speed was 1,636 µm/min (N = 28), maximum, 2800 µm/min (N = 3). This is the fastest speed recorded for a spirochete, and upward of two orders of magnitude above the speed of a human neutrophil, the fastest cell in the body. This alacrity and its interpretation, in an organism with bidirectional motor capacity, may well contribute to difficulties in spirochete clearance by the host.
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0001633
Did you know that borrelia doesn’t need iron to survive?
“All bacterial pathogens described to date have developed specialized systems to acquire iron from their hosts,”said microbiologist Frank Gherardini. “Current dogma states that to be successful in humans, bacteria must overcome strict iron limitations that the human body imparts on them. Although iron is abundant in humans, the amount of free iron is well below the levels required to support the growth of most bacteria. To our surprise, we found that B. burgdorferi doesn’t even require iron. In fact, iron is extremely toxic to it.”
http://www.sciencedaily.com/releases/2000/06/000602073005.htm
Wow, borrelia has 3 times more plasmids than any other bacteria & is more complex than syphilis!
Borrelia has over 1500 gene sequences so this is a very, very complex bacteria. There are at least 132 functioning genes in Borrelia and this is in contrast to Treponema pallidum which is the spirochaete that causes Syphilis. This bacteria has only 22 functioning genes so Borrelia is a much more complex organism from a genetic point of view compared to the organism that causes Syphilis.
Now, in addition, to all of these functioning genes, the structure of Borrelia is quite interesting because it has 21 plasmids and plasmids are these extra chromasomal strands of DNA that are kind of the early response mechanism for bacteria.
http://ticktalkireland.org/didyouknow.html
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Videos on Borrelia bacteria morphology:
http://wn.com/Lyme_disease_microbiology
Includes blebs, spiros, cysts & biomasses.. (see various video links on right of page when loaded)
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Dr. Alan B. MacDonald M.D., Staff Pathologist at the St. Catherine of Siena Medical Center. (published online 10 July 2006 in Volume 67, Issue 4, page 819-832 in Medical Hypotheses)
“Conventional thinking about spirochetal cyst forms is divided between two polar spheres of influence; one a majority community that completely denies the existence of spirochetal cyst forms, and a second group of academically persecuted individuals who accepts the precepts of such antebellum scientists as Schaudinn, Hoffman, Dutton, Levaditi, Balfour, Fantham, Noguchi, McDonough, Hindle, Steiner, Ingraham, Coutts, Hampp, Warthin, Ovcinnikov, and Delamater. Microscopic images of cystic spirochetes are difficult to ignore, but as has been the case in this century, academic “endowments” have nearly expunged all cystic spirochetal image data from the current textbook versions of what is the truth about the spirochetaceae. If the image database from the last century is obliterated; many opportunities to diagnose will be lost. Variously sized cystic spirochetal profiles within diseased nerve cells explain the following structures: Lewy body of Parkinson’s disease, Pick body, ALS spherical body, Alzheimer plaque. Borrelia infection is therefore a unifying concept to explain diverse neurodegenerative diseases, based not entirely on a corkscrew shaped profile in diseased tissue, but based on small, medium and large caliber rounded cystic profiles derived from pathogenic spirochetes which are hiding in plain sight.”
http://www.medical-hypotheses.com/article/S0306-9877%2806%2900275-1/abstract
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