Biofilms ll – Lyme, Pleomorphism and Bacteriophages
Due to the complexity of biofilms and based on the feedback we received to our recent newsletter article on biofilms, we wanted to provide some additional detail on this topic.
First a quick review on what biofilms are:
Here is a short YouTube vide on:
And here is a good visual representation of how biofilms form:
Fig. 1: The biofilm life cycle. 1: individual cells populate the surface. 2: extracellular polymeric substance (EPS) is produced and attachment becomes irreversible. 3 & 4: biofilm architecture develops and matures. 5: single cells are released from the biofilm.
And the significance of biofilms in human infections is substantial:
More than 75% of infections in humans are associated with biofilms. The Center for Disease Control estimates that over 65% of hospital-acquired infections are caused by biofilms.
And we have all dealt clinically with young children who develop chronic infections such as Otitis Media:
The usage of antibiotics in these children can actually help to perpetuate this cycle of chronic biofilm generated infections:
From an article in Science Daily:
Link between antibiotics, bacterial biofilms and chronic infections found
“The link between antibiotics and bacterial biofilm formation leading to chronic lung, sinus and ear infections has been found, researchers report. The study results illustrate how bacterial biofilms can actually thrive, rather than decrease, when given low doses of antibiotics. Results of this study may lead to new approach for chronic ear infections in children”.
(and here is the abstract)
Siva Wu, Xiaojin Li, Manjula Gunawardana, Kathleen Maguire, Debbie Guerrero-Given, Christoph Schaudinn, Charles Wang, Marc M. Baum, Paul Webster.
Beta- Lactam Antibiotics Stimulate Biofilm Formation in Non-Typeable Haemophilus influenzae by Up-Regulating Carbohydrate Metabolism. PLoS ONE, 2014; 9 (7): e99204 DOI: 10.1371/journal.pone.0099204
And as we mentioned in our previous article, the current medical / pharmaceutical approach to addressing biofilms is partly focused on disrupting a communication system utilized by bacteria referred to as “Quorum Sensing”
Here is a representative article referencing this phenomenon:
What is Quorum Sensing and how do bacteria talk to each other?
Another approach is to utilize bacteriophages to attack the bacteria in the biofilm mass. Bacteriophages are viruses that infect bacteria in the same way that they invade human cells.
This treatment modality was actually well developed and utilized in Eastern Europe prior to the advent of antibiotics, but of course it got pushed into the background. This approach is realizing a resurgence of interest due to the issue of antibiotic-resistant bacteria.
Here is a good reference page on Bacteriophages
(by Stephen T. Abedon, Ph.D., Assoc. Prof. Microbiol., The Ohio State University)
Dr. Alex Vasquez did a great webinar (with presentation documentation available) on the importance when dealing with the microbiome of taking into consideration not only the bacterial and viral populations, but also the importance of bacteriophages:
Mitochondrial Dysfunction in Autoimmunity and the Role of Viruses and Bacteria: An Exploration with Lupus as the Prototype
Notes for this: https://www.bioticscan.com/Clinicians-Resources/alex-vasquez
(You must be logged into our website to view)
Biofilms and Lyme Disease
As we all know, once a Lyme infection has settled in, it can become a chronic, difficult to resolve condition which can dramatically impact on a patient’s quality of life.
In large measure, this is because the Lyme spirochete becomes sequestered in biofilm which makes it difficult for anti-microbial compounds to penetrate the biofilm to actually be able to impact on the spirochetes.
And the Lyme spirochetes are incredibly adept at not triggering the immune system and they are very adaptable to changing conditions.
This can be illustrated in the pleomorphic properties of the spirochetes.
Within a single species of organism, this would refer to: (from Wikipedia):
“Pleomorphism, in microbiology, is the ability of some bacteria to alter their shape or size in response to environmental conditions”.
So in other words, microorganisms (including the Lyme spirochete) can respond to a changing terrain in the body (such as pH, oxygen levels) by changing their morphology.
Here is a great short YouTube video illustrating this phenomenon:
A researcher is examining a biofilm with a high powered microscope and in the video they identify approximately ten distinct morphological variations of the Lyme spirochete:
But the traditional concept of Pleomorphism goes beyond just the morphological variability within one species to suggest that microorganisms can actually change from one distinct microbial species to another and from being pathogenic to non-pathogenic, depending upon modulation / variability of the body’s internal terrain.
This concept was originally developed by Gunther Enderlien, and suggests that microorganisms can shift back and forth between being a bacterium to a fungal form to a yeast form.
This concept was further developed by other individuals such as Gaston Naessens in Quebec.
This concept is most typically utilized when Dark Field Microscopy is used as an assessment modality. Several of us here at Biotics have received training in Dark Field Microscopy and have utilized it as a modality in clinical practice, and the video recordings of this phenomenon are quite remarkable.
Here is a link to more information on this concept of Pleomorphism, including some videos.
Therapeutic Approaches to Dealing with Biofilm Conditions
Chronic infections which develop as a result of biofilms represent a challenge for clinicians trying to help their patients.
Certainly the basics that you would cover with everyone are necessary (sleep, stress, gut health (leaky gut, dysbiosis etc.), inflammation, toxin load, hormone levels, heavy metals etc.) – but more specifically for addressing biofilm conditions, we recommend the following protocol considerations:
The Biotics Research A.D.P. (Advanced Dysbiosis Product: Emulsified Oil of Oregano tablet) and Berberine HCl*(Hydrochloride) used together are recommended for Biofilms.
High doses are required for three or four weeks. The highest dose for A.D.P. (gradual work up) is 6 tabs TID, empty stomach is preferred.
Also DDI (Doctor’s Data) Post provocative fecal test using Chela-Zyme (our oral heavy metals chelation formulation) as the provocative challenge (6 BID empty for 7 days, then test)
Toxic metals are always a key factor in pathogenic and Biofilm invasion…
The efficacy of both Oil of Oregano (main active ingredient: Carvacrol) and Berberine for biofilm infections is well documented in the literature:
Here are a couple of representative abstracts:
Applied and Environmental Microbiology
Antimicrobial Action of Carvacrol at Different Stages of Dual-Species Biofilm Development by Staphylococcus aureus and Salmonella enterica Serovar Typhimurium
- R. Knowles1,*, S. Roller1,†, D. B. Murray1,‡ and A. S. Naidu1,§
APMIS. 2012 Dec;120(12):967-73. doi: 10.1111/j.1600-0463.2012.02928.x. Epub 2012 Jul 5.
Enhanced activity of carvacrol against biofilm of Staphylococcus aureus and Staphylococcus epidermidis in an acidic environment.
Nostro A1, Cellini L, Zimbalatti V, Blanco AR, Marino A, Pizzimenti F, Giulio MD, Bisignano G.
Int J Antimicrob Agents. 2009 Jul;34(1):60-6. doi: 10.1016/j.ijantimicag.2008.10.033. Epub 2009 Jan 20.
Effect of berberine on Staphylococcus epidermidis biofilm formation.
Wang X1, Yao X, Zhu Z, Tang T, Dai K, Sadovskaya I, Flahaut S, Jabbouri S.
And once again for reference from our last article on Biofilms is the list of Biotics products which may be of benefit in addressing biofilms:
Biotics offers a range of products which can be of benefit in dealing with biofilm infections: *= High Rating
Beta Plus* Some research indicates that ox bile could have significant antimicrobial effects on antibiotic resistant Staphylococcus Aureus and other dysbiotic pathogenic organisms
References:
Search: Ox Bile and Enterobacteriaceae, Salmonella and Gram Positive enterococci
A.D.P. *(Advanced Dysbiosis Product: Emulsified Oil of Oregano)
Bio-HPF (H. pylori factor)
One of the Physicians who reads our newsletter suggested that he has seen good clinical results for breaking up biofilms by getting his patients to consume sulforaphane compounds (such as is contained in our Biotics NitroGreens product), or as our reader suggested consuming broccoli sprouts.
And of course a precautionary note in this process is the fact that breaking down the biofilm will release microbes and toxic compounds (such as Lipopolysaccharides: LPS) back into general circulation such that one must be cautious of a potential Herxheimer’s reaction:
A good precaution to help to prevent or ameliorate this reaction and discomfort for the patient is to utilize some proteolytic enzymes, such as the Biotics Intenzyme Forte
Biofilm and chronic infections can present a significant challenge in clinical practice today, however there are many natural compounds that are proven to be effective in breaking down and dissolving biofilms so that the individual micro-ogranisms can be more directly dealt with.
Addedum: Methylene Blue for Alzheimer’s
We had some requests for more published research relating to our last article on utilizing Methylene Blue as a treatment option for Alzheimer’s so we have included some additional published research on this topic at the end of this article…
Regards,
Rob Lamberton
Robert Lamberton Consulting
Functional Medicine Consultant – Biotics Canada Products
Certified Light/Darfield Microscopy Nutritionist
Formulator of Professional Nutraceutical Products
Contributing Writer / Advisory Board Member:
Nutricula: The Science of Longevity Journal
Healthy Organic Woman Magazine
Twitter: rob_lamberton Skype: larch60 Facebook: rlamberton
Email: rob@bioticscan.com
Phone: 778-317-4952
Copyright © 2015 R. V. Lamberton & Associates, All rights reserved.
Additional Reference Material on Biofilms
Dr. Tim Lu – Biofilms and Phage Therapy
Nat Prod Rep. 2010 Mar;27(3):343-69. doi: 10.1039/b804469b. Epub 2010 Feb 3.
Quorum sensing and bacterial biofilms.
Indian J Exp Biol. 2013 Sep;51(9):764-72.
Identification of natural compounds which inhibit biofilm formation in clinical isolates of Klebsiella pneumoniae.
Magesh H1, Kumar A1, Alam A1, Priyam1, Sekar U2, Sumantran VN3, Vaidyanathan R1.
Sci Prog. 2001;84(Pt 3):235-54.
Bacterial biofilms and human disease.
Wilson M1.
Curr Pharm Des. 2015;21(1):85-99.
Bacteriophages and their enzymes in biofilm control.
Bacteriophage. 2011 Mar;1(2):66-85.
Phage treatment of human infections.
Abedon ST1, Kuhl SJ, Blasdel BG, Kutter EM.
Biofilm susceptibility to bacteriophage attack: the role of phage-borne polysaccharide depolymerase
Biofilm – The Unseen Protector of Lyme Disease
Published: October 24, 2012
Characterization of Biofilm Formation by Borrelia burgdorferi In Vitro
- Eva Sapi , Scott L. Bastian, Cedric M. Mpoy, Shernea Scott, Amy Rattelle, Namrata Pabbati, Akhila Poruri, Divya Burugu, Priyanka A. S. Theophilus, Truc V. Pham, Akshita Datar, Navroop K. Dhaliwal, Alan MacDonald, David F. Luecke
Link between antibiotics, bacterial biofilms and chronic infections found
- Siva Wu, Xiaojin Li, Manjula Gunawardana, Kathleen Maguire, Debbie Guerrero-Given, Christoph Schaudinn, Charles Wang, Marc M. Baum, Paul Webster
Dr. Tim Lu – Biofilms and Phage Therapy
APMIS Suppl. 2013 May;(136):1-51. doi: 10.1111/apm.12099.
The role of bacterial biofilms in chronic infections.
Methylene Blue and Alzheimer’s Reference Material
J Alzheimers Dis. 2010;20 Suppl 2:S439-52. doi: 10.3233/JAD-2010-100414.
Protective role of methylene blue in Alzheimer’s disease via mitochondria and cytochrome c oxidase.
Methylene blue and memory
http://www.alz.org/research/video/alzheimers_researchers_dickey.asp
PLoS One. 2012;7(10):e48279. doi: 10.1371/journal.pone.0048279. Epub 2012 Oct 31.
Neuroprotective actions of methylene blue and its derivatives.
Poteet E1, Winters A, Yan LJ, Shufelt K, Green KN, Simpkins JW, Wen Y, Yang SH.
Researchers decipher modus operandi of potential Alzheimer’s drug
- Copyright © 2015 R. V. Lamberton & Associates, All rights reserved.
Angew. Chem. Int. Ed., 52: 3511–3515.
Mechanistic Basis of Phenothiazine-Driven Inhibition of Tau Aggregation
Akoury, E., Pickhardt, M., Gajda, M., Biernat, J., Mandelkow, E. and Zweckstetter, M. (2013)
- Copyright © 2015 R. V. Lamberton & Associates, All rights reserved.
APMIS. 2012 Dec;120(12):967-73. doi: 10.1111/j.1600-0463.2012.02928.x. Epub 2012 Jul 5.
Neuroprotective Actions of Methylene Blue and Its Derivatives
Ethan Poteet, Ali Winters, Liang-Jun Yan, Kyle Shufelt, Kayla N. Green, James W. Simpkins, Yi Wen, Shao-Hua Yang
And some interesting thoughts from an article on Examiner.com
Other non-clinical research has enhanced the credence to the notion that methylene blue may be a wonder drug for not just treating Alzheimer’s disease but other neurodegenerative diseases. For instance, many tissue culture studies have shown that methylene blue can reversed the aggregation of tau, a protein that forms toxic aggregates called senile neurofibrillary tangles in Alzheimer’s disease brain tissue, in different neuronal cell lines and enhance neuronal survival.
Moreover, methylene blue can destroy and dissolve toxic aggregates formed by amyloid beta, another protein that is aggregated in Alzheimer’s disease, in neuroblastoma cell lines and improves neuronal survival. Interestingly, other research suggests that methylene blue may be a general anti-protein aggregate buster since other tissue culture studies show that this wonder compound also inhibits the aggregation of TDP-43, a protein that forms the major component of inclusions aggregates in amyotrophic lateral sclerosis and in frontotemporal degeneration. In other word, methylene blue may have other medical applications to treat many other neurodegenerative diseases.
Remarkably, the biological effects of methylene blue does is not limited to its anti-protein aggregate activity but has been shown to improve the function of mitochondria in neurons.
Remarkably, methylene blue is able to enhance mitochondrial function, delay cellular senescence (aging) by enhancing the activity of antioxidants and promotes survival under basal conditions in fibroblasts . In other words, this study
shows that methylene blue acts as an anti-oxidant by sequestering free radicals released by mitochondria and somehow restores mitochondrial respiration at the level of complex I and IV.
These remarkable results show that methylene blue may possibly delay dementia and cognitive decline in Alzheimer’s disease patients by improving mitochondrial function in neurons and by acting as a plaque and tangle buster by dissolving toxic tau and amyloid beta aggregates.
Methylene blue and Alzheimer’s disease
Murat Oza, b, , , Dietrich E. Lorkec, George A. Petroianub
Takashi Mori1, Naoki Koyama1, Tatsuya Segawa2, Masahiro Maeda2, Nobuhiro Maruyama2, Noriaki Kinoshita2, Huayan Hou3, Jun Tan3 and Terrence Town4*
We will be doing a more extensive newsletter article on Alzheimer’s in the near future, however in the interim here are a few key Biotics products that are of benefit as part of a comprehensive Alzheimer’s Protocol:
- Chela-Zyme (Oral Heavy Metals Chelation)
- CoQ-Zyme 100 Plus (Emulsified CoQ10 – activates AMPK)
- Dismuzyme Plus 5000 (High Potency SOD/Catalase)
- Intenzyme Forte (Proteolytic Enzymes)
- KappArrest (NF-kappa B – Activates AMPK)
- Copyright © 2015 R. V. Lamberton & Associates, All rights reserved.
- Berberine HCl (Activates AMPK)
- Lipoic Acid Plus (Alpha Lipoic Acid – Activates AMPK)
- Nutri-Clear (Phase 1 & ll detox, activates AMPK)
- Lipid-Sirt (Dyslipidemia – Activates AMPK)
- And many others…