A cause of persistent infections
Tick-borne diseases pose a significant threat to human health, with the number of cases rising threefold in the U.S. in recent years. The most common tick-borne illness is Lyme disease. According to a recent estimate, approximately 476,000 Americans are diagnosed and treated for Lyme disease each year.
Lyme disease is caused by a spiral-shaped bacterium (spirochete) known as Borrelia burgdorferi, which is transmitted through the bite of a tick. Ticks can also transmit other bacteria and parasites, and co-infections with Borrelia are common.
Lyme disease is associated with fatigue, arthritis, and neurological symptoms that can persist for months to years after the initial infection. The lingering presence of biofilm may contribute to the persistence of Lyme disease symptoms. In this post we’ll explore some intriguing strategies for remedying biofilms, including the use of serrapeptidase, trypsin, alpha-lipoic acid, and EDTA.
What is biofilm?
Biofilms begin with microbial cells that adhere to a surface, such as the lungs, urinary tract, heart, or a medical implant. Once they attach, the microbes surround themselves with a thick, slimy coating comprised of proteins, polysaccharides, and other biopolymers, forming a semi-permanent colony.
The biofilm matrix (slime) serves as a safe house or bunker that shields the microbes from antibiotics and the immune system., In fact, biofilms have been described as the most successful life forms on Earth.
Unfortunately, biofilm-residing bacteria are highly resistant to both the immune system and to antibiotic treatments., It’s no wonder that 80% of all chronic infections are associated with biofilm.
Antibiotics generally kill only free-floating bacteria, and they do not eradicate biofilm. In Borrelia biofilms that were treated with strong antibiotics, live bacterial cells were still found within 70% to 85% of the biofilm colonies.
Lyme disease and biofilm
Most patients recover from tick-borne infections if antibiotic treatment is begun immediately after the tick bite. However, if the infection is not treated right away, Borrelia can disseminate throughout the body, including sites like the joints, heart, and brain. This generally happens within two weeks of the bite of an infected tick.,,,
Up to 20% of individuals who are treated for Lyme disease with a course of antibiotics will go on to experience chronic fatigue, musculoskeletal pain (including arthritis), neurological ailments including neuropathy, and depression., One or more of these symptoms may persist for months or even years after the initial infection.
Although there is controversy about the reasons for post-treatment Lyme disease syndrome (PTLDS), many scientists believe that biofilms are to blame.,, Biofilms are not only resistant to antibiotics, but they also cause more severe inflammation and arthritis than actively-growing “planktonic” bacteria. Also, by staying dormant and hidden from the immune system, the biofilm bacteria may later emerge to produce acute infections.
Natural and/or synthetic substances are needed that can safely disperse biofilms and improve the efficacy of treatments for Lyme disease and other infections., Let’s take a closer look at the current research using serrapeptidase, trypsin, alpha-lipoic acid, and EDTA to break up biofilms.
The biofilm matrix contains an array of bacterial proteins., Logically, enzymes that degrade proteins may help bust up biofilm. One of the most promising anti-biofilm enzymes is serrapeptidase (also known as serratiopeptidase, serralysin, or SPEP).
SPEP can help disrupt biofilm by removing proteins that adhere biofilm to host cells.
SPEP is an enzyme made by Serratia, a bacterium found in the digestive tract of many species. SPEP was first isolated in 1970 from silk worms. The enzyme plays an important role in the silk worm intestine, allowing the emerging moth to digest and dissolve its cocoon. Similarly, SPEP can help disrupt biofilm by removing proteins that adhere biofilm to host cells.,,
SPEP also increases the efficacy of antibiotics in live bacterial cultures,,,,, and it enhances the penetration of antibiotics into living tissues.,, A detailed investigation concluded that the use of SPEP could represent a viable option for the development of novel combination therapies.
The scientists who first discovered SPEP showed that the enzyme has systemic mucolytic (mucus-degrading), fibrinolytic (fibrin-degrading), and anti-inflammatory activity.,, Oral SPEP formulations have especially been used to loosen mucus and improve symptoms in individuals with the common cold, sinusitis, bronchitis, and other respiratory conditions.,,
SPEP also reduces inflammation associated with soft tissue injuries, and it helps clear out debris and dead cells that are by-products of the healing process after surgery.,,,, The anti-inflammatory properties of SPEP may also prove useful for biofilm infections, since persistent biofilms trigger inflammation.
Trypsin is a proteolytic enzyme secreted by the pancreas. It breaks down proteins in the small intestine, releasing peptides and amino acids that can be absorbed. For people with pancreatic insufficiency who have low enzyme levels, oral enzyme supplementation is used to aid digestion.,
A portion of the active trypsin enzyme is absorbed intact, enters the bloodstream, and circulates throughout the body.,, Oral formulations of trypsin (along with an enzyme called chymotrypsin) have been used clinically to hasten the repair of surgical, orthopedic, and burn injuries. The enzymes were shown to help break down damaged cells and necrotic material.,,
In laboratory studies, trypsin was shown to alter the stability, adhesion, and biofilm-forming ability of various bacterial species.,, One study investigated the effect of trypsin on P. aeruginosa, a bacterium that forms biofilms in wounds, lungs, and other organs., Trypsin disrupted the P. aeruginosa biofilm without harming human cells, and it lowered the concentration of antibiotics needed to kill the bacteria.
In a study of Escherichia coli, the main culprit in urinary tract infections, trypsin removed bacterial surface proteins that stabilize biofilm and reduced the viscosity of the matrix, causing the biofilm to disintegrate.
In a study of Borrelia, which causes Lyme disease, incubation of the spirochetes with trypsin also caused a loss of bacterial surface proteins. This significantly reduced the attachment of the bacteria to human cells, suggesting the potential to disrupt an early step in biofilm production.
Trypsin was shown to degrade a Borrelia protein known as NapA (neutrophil attracting protein A) which is a key player in Lyme disease symptoms and severity.
Trypsin also was shown to degrade a Borrelia protein known as NapA (neutrophil attracting protein A) which is a key player in Lyme disease symptoms and severity. NapA triggers inflammation and plays an important role in the arthritis-inducing effects of Borrelia.,,, The evidence suggests that trypsin might help disrupt biofilm and reduce tissue inflammation.
Alpha lipoic acid
Alpha-lipoic acid (ALA) is a powerful antioxidant that regenerates other antioxidants, such as glutathione. It helps protect tissues from various forms of oxidative damage, and is used worldwide as a natural supplement for this purpose.,,, ALA also has metal-chelating activity that may contribute to its anti-biofilm effects.,
Infections trigger the depletion of glutathione, the master antioxidant in cells., Low glutathione levels cause oxidative stress, a redox imbalance that signals microbes to shift from a free-floating form to a biofilm-forming mode., Subnormal glutathione levels have been shown to enhance biofilm production and to increase the severity of infections.,,
ALA replenishes glutathione and helps protect neurons from oxidative damage, which is an important consideration when it comes to Lyme disease.
ALA replenishes glutathione and helps protect neurons from oxidative damage, which is an important consideration when it comes to Lyme disease.,, Higher glutathione levels help boost the activity of immune cells that control bacterial infections.,,
Glutathione may also disrupt biofilms directly, and improve antibiotic efficacy. ALA also has moderate antimicrobial and antibiofilm effects on its own. In a study of Cronobacter sakazakii, a bacterium that can cause sepsis and meningitis, the addition of ALA reduced bacterial proliferation. With P. aeruginosa, ALA was shown to inhibit biofilm formation without altering bacterial growth.
Ethylenediaminetetraacetic acid (EDTA) is a chelator that is used for the treatment of lead toxicity, as it binds lead and other divalent cations (including calcium, discussed below.) More recently, EDTA is gaining interest as a “slime dispersant” that may increase the efficacy of antibiotics against biofilm.
A combination of EDTA and gentamicin successfully killed 100% of the biofilm bacteria.
Calcium is a divalent cation that hardens the biofilm matrix and makes it resistant to antibiotics. This occurs in part because calcium binds to alginate, a biofilm component produced by many pathogens, including Borrelia and P. aeruginosa. , The combination of calcium with alginate produces a highly cross-linked and rigid biofilm that is difficult for antibiotics to penetrate.,
By chelating calcium, EDTA destabilizes the biofilm matrix and causes bacterial cells to detach, making them more susceptible to antibiotics., In culture, EDTA treatment of P. aeruginosa biofilms reduced the number of biofilm-associated cells by >99%, while the antibiotic gentamicin caused a reduction of <10% in the number of biofilm cells. A combination of EDTA and gentamicin successfully killed 100% of the biofilm bacteria.
In a study of biofilm infections in wounds, scientists concluded that “EDTA could provide an essential tool to manage biofilm-related infections and should be considered as an anti-biofilm agent alone or in combination with other antimicrobials or technologies for increased antimicrobial performance.” Of course, clinical studies are needed to confirm these findings in the case of Lyme disease and other systemic infections.
In sum, serrapeptidase, trypsin, alpha-lipoic acid, and EDTA have been shown to disrupt biofilm complexes, reduce oxidative stress and inflammation, and improve antibiotic penetration into biofilm complexes in laboratory and animal studies. These four bioactive compounds are orally available, have a history of clinical use for various indications, and may be useful as adjuncts to standard treatments for the management of stubborn infections.Click here to see References
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