Tincup
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Front Microbiol. 2016 Feb 10;7:62. doi: 10.3389/fmicb.2016.00062. eCollection 2016.
Eradication of Biofilm-Like Microcolony Structures of Borrelia burgdorferi by Daunomycin and Daptomycin but not Mitomycin C in Combination with Doxycycline and Cefuroxime.
Feng J1, Weitner M1, Shi W1, Zhang S1, Zhang Y1. Author information
1Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore MD, USA.
Abstract
Lyme disease, caused by Borrelia burgdorferi, is the most common vector-borne disease in the United States and Europe.
While the majority of Lyme disease patients can resolve their symptoms if treated promptly, 10-20% of patients suffer from prolonged symptoms called post-treatment Lyme disease syndrome (PTLDS).
Although the cause for PTLDS is unclear, one possibility is the presence of bacterial persisters not effectively cleared by the current Lyme antibiotics.
Recent studies identified several drug candidates including daptomycin, daunomycin, doxorubicin, and mitomycin C that had good activity against B. burgdorferi persisters.
However, their relative activities against B. burgdorferi persisters have not been evaluated under the same conditions.
In this study, we tested the anti-persister activities of these drugs against both 7-day and 15-day old stationary phase cultures of B. burgdorferi individually as well as in combination with Lyme antibiotics doxycycline and cefuroxime (Ceftin).
Our findings demonstrate daunomycin and daptomycin were more active than mitomycin C in single drug comparison at 10 and 20 μM, as well as in drug combinations with doxycycline and cefuroxime.
In addition, daunomycin was more active than doxorubicin which correlated with their ability to stain and accumulate in B. burgdorferi.
The two drug combination of doxycycline and cefuroxime was unable to eradicate biofilm-like microcolonies of B. burgdorferi persisters.
However, the addition of either daunomycin or daptomycin to the doxycycline + cefuroxime combination completely eradicated the biofilm-like structures and produced no visible bacterial regrowth after 7 and 21 days, while the addition of doxorubicin was unable to prevent regrowth at either 7 or 21 day subculture.
Mitomycin C in combination with doxycycline and cefuroxime caused no regrowth at 7 days but visible spirochetal regrowth occurred after 21 day subculture.
Furthermore, we found that cefuroxime (Ceftin), the third commonly used and most active antibiotic to treat Lyme disease, could replace cefoperazone (a drug no longer available in the US) in the daptomycin + doxycycline combination with complete eradication of the biofilm-like structures as shown by lack of any regrowth in subcultures.
Our findings may have implications for improved treatment of Lyme disease. KEYWORDS:
Borrelia burgdorferi; anti-persister activity; biofilm; drug combination; persister
Jordana
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I saw this but searching this board it doesn't seem like anyone did well on Daptomycin. Big herx, no payoff.
I sometimes think some of these guys are overimpressed with herxes.
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Keebler
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- Their failure to consider the forms of Bb is of great concern to me, particularly the cystic form which they are doing nothing about.
They seem stuck on just one part of the puzzle with a simplistic view of the landscape, including coinfections.
What they are looking as is important, however, their focus is far too narrow and even more dangerous as they don't even know it. -
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Tincup
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You two shock me saying this stuff. Really. This is by far the biggest and greatest step forward we've had in 40 years.
We are learning what will actually kill Borrelia in the lab, what exactly it will take. This is groundbreaking stuff never before done by anyone ever (with Eva also working on it too).
Till now it has been a guessing game with all of us as the guinea pigs.
Keebler said.. "Their failure to consider the forms of Bb is of great concern to me, particularly the cystic form which they are doing nothing about."
They already did that study and used the few meds that were most effective in killing ALL forms to do this next study you see above. They are honing in on the actual cure (in the lab) if a cure is possible. The it can be tested on humans.
I will assume once they know what meds are best for killing all forms of Lyme without "regrowth" or complications then someone can make "a pill" with all of the proper antibiotics combined into one (or something similar).
PLUS, they are proving that doxy isn't getting it at all, refuting all of the IDSA/CDC and insurance bull that we've been smothered under for so long.
They've already proven the IDSA guidelines (new ones coming out) are wrong if they stick with the same old same old. So they are coming close to the cure and blocking the trash from building up at the same time.
AND, it helps to discourage the need for a new vaccine that we all know won't work and that will hurt more people. And doing it scientifically.
This is history in the making and I am thrilled to see it. Totally thrilled.
Tincup
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As far as the coinfections- good news there too. Once we have the right combo for Lyme (all forms), they can test it on each of the coinfections, one at a time, and add to or take away from the formula as needed.
In other words, if one antibiotic actually kills Ehrlichia and RMSF too, and that is ONLY doxy right now, maybe a combo new drug can hit all three (Lyme, et al). And how nice would that be?
And in our lifetime we still may not have all of the answers and access to these meds, but our future generations will and the millions who will get Lyme, etc. from now on could.
Jordana
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I agree with everything you've said, Tincup; and it does point to a more sophisticated view of borrelia.
In fact I think it's interesting that they're now turning to leprosy and TB drugs to see how they do.
I was just pointing out that people who've written here that they were on it didn't have a good experience. In fact one big problem with borrelia is that almost all tested therapies are extremely hard to tolerate and there are a lot of people who just can't ( or wouldn't) live through it.
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posted
So it sounds like these new drugs are being tested in the lab and not used by patients yet?
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hiker53
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At least it is one step closer.
I can't wait to see if it is effective on Lyme patients who were not diagnosed quickly.
-------------------- Hiker53
"God is light. In Him there is no darkness." 1John 1:5 Posts: 8879 | From Illinois | Registered: Aug 2004
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Tincup
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Hiker hit the nail on the head. Will it help CHRONIC patients? We don't have a clue yet. We know we (as chronic patients) are more Lyme and coinfections than human at this point, so how will it be for us compared to those who are recently infected?
J said the treatment with these drugs is hard on people, and I agree. But WHY are they hard?
Since this is ONLY being tested in the lab, there may need to be adjustments. Surely there will be.
Could it be the same drugs people are "trying" here now (that J is reading about) are way too powerful since it IS killing the organisms (rather than playing peek a boo like other antibiotics do) and all that is needed is a sliver of a full dose daily or even once a week?
We don't have all the answers yet, but this is the first time anyone has taken a pantry full of misc. products and tried using them to kill various forms of Borrelia and ALL forms.
Jordana
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Yes, why are they hard?
This is something I really don't understand about this whole phenomenon.
You have spirochetes in you; you have weird and horrifying symptoms. But the spirochetes aren't being killed by the immune system - the immune system can't see them.
Then you take the abx and kill spirochetes - NOW the symptoms intensify because of "dieoff." Well, they weren't dying before so how were they creating symptoms when they were alive and undetected?
There's something missing in the explanation of this I think.
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TF
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In many people, the immune system CAN see the spirochetes and is killing them. But, if you take steroids or have surgery, etc. the immune system suddenly cannot keep up with the spirochetes and so you begin exhibiting symptoms for the first time, even though the bite was in the past.
These folks will have positive bands on the Western Blot.
Some people get such a germ load right off the bat that their immune system cannot keep the lyme in check and so they get symptoms immediately after the bite.
Six or so weeks after the bite, they may also get a positive Western Blot because they are making some antibodies to the lyme, just not enough to keep it in check.
So, in only some cases of lyme is the immune system totally clueless as to the presence of the bacteria. Lyme is a bacteria and so it causes symptoms just like other bacteria are able to cause symptoms.
Lyme has many ways of evading the immune system. One is to cloke itself with the body's own cells, another is to hide in biofilms, etc. But, generally ALL of the lyme is not invisible to the immune system all of the time.
So, if a person is tested by a good lab like Igenex and if the doc who gets the test results knows what he is doing, generally the person will get some positive (or weakly positive) bands which indicates the presence of lyme antibodies. A lyme literate physician will then treat the person for lyme.
Regarding how the lyme bacteria can cause symptoms, well first the immune system IS killing lyme in many cases. But, even if it weren't killing lyme at all, when lyme gets into the brain, it causes inflammation of the arteries, tissues, etc. This leads to lack of sufficient bloodflow to the brain. That causes many of the mental symptoms we experience (memory problems, brain fog, etc.) The symptoms vary depending on which parts of the brain are attacked by the lyme bacteria.
When the body forms plaques to protect the brain from the lyme, the plaque itself causes Alzheimer's symptoms.
When the lyme attacks peripheral nerves, it causes them not to be able to function properly. So, you get the various neuropathies that lyme patients experience. Perhaps the lyme inflames the nerves, or deteriorates the myelin sheath, or the nerve itself, etc.
When the lyme attacks the ovaries, they cannot function properly. It makes them shut down. The ovaries shrivel and become inoperative. Then, the various symptoms of menopause occur due to lack of essential hormones.
I don't think we know enough to say exactly WHAT the lyme does to shut down the ovaries. The ovaries appear to doctors to be normal, just very small, consistent with menopause. Yet, when the lyme is treated, the ovaries come back to normal size and begin functioning again.
Lyme affects whatever organ it invades--thyroid, etc. In the brain, it affects the sleep center so that the person cannot sleep normally.
Lyme is found in the fluid in the joints. Evidently it causes inflammation in the joints so that the knee may swell and any affected joints will hurt.
When lyme attacks the facial nerves, you can get Bells Palsy, trigeminal neuralgia, etc. These nerves become paralyzed or fire inappropriately. Perhaps someone has studied how the lyme does this, but we know it does it.
Whatever system of the body lyme attacks, that system can no longer function properly. So, that is how lyme causes symptoms even in people whose immune systems have no clue that the lyme is there.
Because lyme causes inflammation in the victim, at least one lyme doctor has advised patients to eat an anti-inflammation diet as part of their lyme treatment.
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TF
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Read pages 3-6 of Burrascano Guidelines. They list a number of ways in which lyme causes its symptoms--lyme depletes the body of magnesium, thus causing symptoms.
It also has "deleterious effect on the hypothalamic-pituitary axis."
"Activation of the inflammatory cascade has been implicated in blockade of cellular hormone receptors." (page 6)
And, "(Bb has been demonstrated in vitro to both inhibit and kill B- and T-cells, and will decrease the count of the CD-57 subset of the natural killer cells). As a result, not only is the infection with Bb perpetuated and allowed to advance, but the entire issue of co-infections arises."
An immune system weakened by lyme will lead to many other problems, just like in AIDS patients. Viruses can reactivate, etc.
So, these are some other ways that lyme destroys the body and leads to hundreds of symptoms which vary from patient to patient.
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bluelyme
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So dapto ,ceftin and doxy iv ...what doc would do this ? Trials?
-------------------- Blue Posts: 1539 | From southwest | Registered: Dec 2015
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Jordana
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Dr. H is already doing it.
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Jordana
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Sorry I missed your reply TF.
The thing is, Lyme is not attacking anything. It's not trying to kill us. It *will*, but all it's trying to do is eat and live. It "hides" in various tissues it finds comfortable, like collagen and synovial fluid. What it "eats" appears to be sugar, so it apparently doesn't metabolize the collagen it's hiding in.
I think the reason it likes the brain and nervous system is because both of these connected organ systems have a high sugar uptake.
Apparently it uses the immune system to get around as it hides inside of white blood cells.
I would be more convinced that it's depleting us of minerals, confusing the immune system and blocking nerve communication which as a result wreak havoc on all kinds of organ systems; not that we're being directly "attacked. " Nerves do not like being invaded and are pretty unhappy also when they lack the electrolyte they use for muscle communication.
The point I'm making is that these things really shouldn't be causing some massive inflammatory response when they die. The only thing I can think of is that they're hidden from the immune system when they're alive; but when they're dead the immune system goes ballistic because they're now visible to it.
Maybe pulsing is really the way to go in that case. I read about people herxing hard for three years straight and I wonder if that's really necessary.
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Tincup
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BORRELIA NEUROTOXIN
Two groups have reported evidence that Borrelia, like several other bacteria, produce neurotoxins.
These compounds reportedly can cause many of the symptoms of encephalopathy, cause an ongoing inflammatory reaction manifested as some of the virus-like symptoms common in late Lyme, and also potentially interfere with hormone action by blocking hormone receptors.
At this time, there is no assay available to detect whether this compound is present, nor can the amount of toxin be quantified. Indirect measures are currently employed, such as measures of cytokine activation and hormone resistance.
A visual contrast sensitivity test (VCS test) reportedly is quite useful in documenting CNS effects of the neurotoxin, and to follow effects of treatment. This test is available at some centers and on the internet.
It has been said that the longer one is ill with Lyme, the more neurotoxin is present in the body. It probably is stored in fatty tissues, and once present, persists for a very long time.
This may be because of enterohepatic circulation, where the toxin is excreted via the bile into the intestinal tract, but then is reabsorbed from the intestinal tract back into the blood stream. This forms the basis for treatment.
TF
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Tincup, feel free to use whatever you like that I have said.
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Jordana
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Thanks Tincup.
I have honestly looked high and low for evidence that there really is such a thing as bbtox1. There is only one paper I can find from 2002 that references it as "identified."
I'm not necessarily saying it's not there, but it seems like it's more theoretical.
It's endlessly frustrating to me how long this thing has been around and how little we know about it.
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Keebler
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- Whatever Bbtox1 is or whoever coined that term -I'd forget looking for that label and study the biochemistry of it for a fuller view. There is no doubt that borellia is very neuro-toxic.
In addition to the toxicity of it, there are ways that lyme attacks and destroys tissue, bone, etc. It's particularly dangerous to the myelin sheath around nerve fibers.
Biochemistry of Lyme Disease: Borrelia burgdorferi Spirochete/Cyst
by Prof. Robert W. Bradford and Henry W. Allen
Townsend Letter - February / March 2006
Excerpt:
Lyme Disease Toxin
Because many of the symptoms of Lyme disease involve the nervous system, it was speculated that the spirochete produced a toxin that disrupted normal nerve function.
Through the use of DNA manipulations and a database of known protein toxin DNA sequences, a match was made with a selected Borrelia burgdorferi (Bb) gene and a specific toxin in the database.
Protein generated from this cloned Bb gene was examined biochemically and found to have characteristics similar to that of botulinum, the toxin of Clostridium botulinum, a zinc endoproteinase.1 -
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Keebler
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The Biology of Lyme Disease: An Expert's Perspective
26 minute YouTube video - Jul 20, 2013
This is a 30 minute video with Dr. Alan MacDonald, a retired M.D. and board certified in Anatomic Pathology and Clinical Pathology. This revealing interview from May 2013 (1 of 3) covers many of the controversies associated with Lyme disease: -
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Jordana
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I don't think it's enough to go through a DNA database and look for protein sequences in Borrelia that match known neurotoxins.
If there was a paper that stated: " We examined neuroborreliosis patients and found evidence that SNAP-25 was being cleaved at the neuromuscular junction and blocking acetylcholine receptors," then I would totally recant. Posts: 2057 | From Florida | Registered: Feb 2015
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Keebler
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- There is no single paper that is going to cover all the bases. Not one. All pieces of a puzzle. Each has detail that can help us as we move forward. -
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Jordana
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I have the same philosophy Keebler and agree Posts: 2057 | From Florida | Registered: Feb 2015
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