Medical researchers and Lyme-literate doctors have known for some time that co-infections complicate the recovery from Lyme borreliosis and in some cases prevent it but the reason for such difficult complications was unclear.
After the discovery of the role of biofilms in Lyme disease by the retired Dr. MacDonald, subsequent research has uncovered evidence of communication within the biofilm between different pathogens that may illuminate the key factors of the problem and hopefully lead to reliable solutions.
The National Institutes of Health estimates that 60% of all human infections and 80% of refractory infections (def. unresponsive to medical treatment) are attributable to biofilm colonies.
- The protection conferred upon microorganisms by biofilm allows them to achieve a high level of antibiotic resistance, stealth and invisibility.
- Biofilm not only provide a physical barrier to antimicrobial agents (pharmaceutical antibiotics) and host antibodies, but facilitate the exchange of antibiotic-resistant genetic material between organisms and may contain antibiotic-degrading enzymes.
- In fact, biofilm communities can be 1000 times more resistant to antibiotics than free-floating bacteria.
- The decreased growth rate of sessile microorganisms (def. Permanently attached to a substrate; not free to move about; “an attached oyster”) also reduces their antibiotic susceptibility as most antimicrobial agents require rapid cell growth in order to effectively kill or inhibit the microbes. Biofilm thus render pathogenic microorganisms enormously difficult to eradicate, and can almost single-handedly contribute to localized or systemic inflammatory reactions and delayed wound healing.
- Depending on the type of biofilm, one or more species of pathogens may be found embedded in the extracellular polymeric substance (EPS). Bacterial EPS maybe a carrier of, or may have heavy metals embedded in them which may require chelation.
Pathogenic bacterial known to reside in biofilms include, but are not limited to: Borrelia burgdorferi (Lyme bacteria), Escherichia coli, Candida albicans (yeast and fungal mutation), Clostridium difficile, Clostridium perfringens, Helicobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella typhimurium, Staphylococcus aureus, Staphylococcus epidermidis, and Vibrio cholerae.
The number of human diseases shown to be associated with biofilms is ever expanding and includes: chronic bacterial prostatitis, chronic rhinosinusitis (chronic sinus infections), cystic fibrosis pneumonia, infective endocarditis, periodontitis, recurrent otitis media, and virtually all device and implant related infections. Strong evidence is also beginning to emerge for an etiologic (causative) role of pathogenic mucosal biofilm in gastrointestinal diseases, such as Irritable Bowel Disorders (IBS): Crohn’s disease and ulcerative colitis.
Biofilms can be composed of multiple species of pathogens.
Lyme biofilms are composed of the covering of the biofilm which forms a matrix rich in sugars, called extracellular polymeric substance (EPS). In addition to polymers, it is composed of extracellular DNA, proteins that are expressed by the pathogens, polysaccharides, metals, and minerals such as calcium, magnesium and iron.
Lyme bacteria exhibit a double cell membrane envelope structure (with an outer and inner membrane ). However, the structure of the spirochete envelope is significantly different from the typical double membranes of gram-negative bacteria . At this time (2011) the outer membrane of Borrelia is determined to be fluid-like, and it is composed of 45-62% proteins (high in lipoproteins), 23-50% lipids (high in glycolipids), and 3-4% carbohydrates.
Lipoproteins (made of proteins and lipids) in Borrelia play a major role in the inflammatory response within the infection sites in the body. One of the functions of the lipoprotein is that it acts as an adhesion in order that the organism can stick to surfaces. Unfortunately the organism itself appears to have a pump system, whereby substances that are internally toxic to it may be removed – these substances include detergents, bile salts, antibiotics, dyes, and heavy metals.
Biofilm pathogens talk to each other
According to the massive textbook “Borrelia: Molecular Biology, Host Interaction and Pathogenesis” recently published by Caister Academic Press, biofilms act like an intelligent community of pathogens, and embedded pathogens appear to have a signaling communication system. Bacteria can produce chemical signals (“talk”) and other bacteria can respond to them (“listen” in a process commonly known as cell-cell communication or cell-cell signaling. This communication can result in coordinated behavior of microbial populations.The pathogens aggregate together, then signal one another to secrete the sticky, protective covering and express proteins. As biofilms stick to the tissue, inflammation and tissue damage occur.
Biofilm communication was first discovered in the 1970s, when scientists at Harvard University and Scripps Institute of Oceanography began to report on a unique and fascinating phenomenon. The system they were investigating was the production of bioluminescence by the marine bacterium Vibrio fischeri (then called Photobacterium). As a result of extensive studies, scientists Nealson, Platt and Hastings published their findings which indicated that the bacteria was “estimating” their population density, which of course implied that they were in communication with one another. In 1970 the idea was absurd to mainstream science but today it is commonly accepted phenomena known as “quorum sensing”.
Montana State University (blog picture courtesy of Montana State University) has a National Science Foundation Engineering Research Center that focuses exclusively on biofilms. They have found that each of the quorum sensing mechanisms they have examined is highly individualized to the specific bacterium possessing it.
Bonnie Bassler at Princeton University explains that this “census-taking” enables the group to express specific genes only at particular population densities. Quorum sensing is widespread; it occurs in numerous Gram-negative and Gram-positive bacteria. In general, processes controlled by quorum sensing are ones that are unproductive when undertaken by an individual bacterium but become effective when undertaken by the group.
She has also discovered that in addition to their “private languages”, many bacteria have developed generalized chemical messages that can be interpreted by members of other species. In lectures she postulates that in the future, we can hope to develop microbes that can “turn-on” good behavior and “turn-off” bad behavior.
For scientists in the biofilm community this information is like a lightning bolt that has sparked numerous implications in medicine. For those of us with chronic Lyme, some believe that this may explain why and how co-infections stall or prevent recovery from our unique “Lyme soup.”
RESOURCES: University of Montana, Borrelia: Molecular Biology, “Host Interaction and Pathogenesis” by Caister Academic Press, Princeton Department of Molecular Biology, Klaire Labs