Hyperthermia, Borrelia (Lyme) and BiofilmsJanuary 29, 2019
Bacterial infections are responsible for over two million severe illnesses in the United States and are responsible for about 23 000 deaths annually.(1)
A review published by Taylor Ibelli et al defined hyperthermia therapies as elevated temperatures applied locally, regionally, or to the whole body, for specific time intervals, that are routinely utilized in current medical practice. Most studies revolve around hyperthermia treatments for oncology; however, recent studies have indicated that similar benefits are possible in the realm of treating local or systemic bacterial infections.(2)
This review demonstrated the tremendous potential of hyperthermia for mitigating bacterial infections and foster new research ventures to help remedy these challenging occurrences.
Biofilm formation occurs when multiple bacteria adhere to a surface and envelop themselves in polysaccharides, proteins, DNA and RNA to produce material that provides a structural extracellular matrix, which protects against antibiotics, immune system responses or other foreign invaders.(2)
Biofilms consist in a polysaccharide shell on the surface that protects the organisms inside from starvation, drying out, the immune system, and antibiotics. Once the organisms are safe inside the biofilm, they can communicate among themselves, a phenomenon called quorum sensing, and is accomplished by signaling molecules. The biofilm is, now, an organism itself, that grows by cell division, and a community of bacteria where different groups play specialized roles of performing metabolic functions for the entire unit.(3)
Fig. 1 – The five stages of biofilm development are (1) initial attachment, (2) irreversible attachment, (3) maturation I, (4) maturation II, and (5) dispersion. (3)
According to Taylor Ibelli et al, researches have observed that hyperthermia plus antibiotic was shown to be more effective for reducing biofilm mass and bacterial colonies. The authors concluded that their results support application of adjuvant hyperthermia in treating infections stemming from medical implants.(2)
Interestingly, Borrelia burgdofei can make biofilms (3, 4, 5) and biofilms can become resistant to antibiotic. As highlighted in Taylor Ibelli et al review, hyperthermia offers new mechanisms for removing bacteria, by disrupting the structural integrity of biofilms, which may benefit the effectiveness and access of antibiotics.(2)
A study performed in 1985 demonstrated that elevated temperatures inhibit bacterial proliferation and mobility, which in turn, can increase autolysis and cell wall damage.(6) The review, along with the study of Mackey et al., confirms that heat increases the permeability of prokaryotic cells.(2, 7) Current hyperthermia techniques may be able to manage into the realm of treating bacterial infections, specifically in managing biofilm-related maladies.
Considering Borrelia biofilm, studies have indicated that temperature is an important regulator of its development, and that the mammalian physiological temperature favors increased biofilm formation in vitro.(4) Moreover, results from a study published in 2015 suggest that biofilm formation might be a common trait of Borrelia genera physiology, which could confer survival advantages during unfavorable conditions.(8)
Even though when it comes to biofilms, Borrelia can join the party, once inside the biofilm, it would lose its ability to manipulate the immune system and therefore lose its capacity to cause symptoms. That said, in a first moment biofilms are not how Borrelia causes illness. However, when it comes to PLTDS, a late immune dysfunction reaction caused by Borrelia, can occur if biofilms in the body flourish. As to whether biofilms prevent antibiotics from eliminating Borrelia, other factors play a greater role in determining antibiotic resistance. Borrelia grows very slowly, exists in small concentrations in the body, can bore deeply into cartilage and brain tissue, and can live inside cells—all factors that enhance resistance to antibiotic therapy.(3)
- Antibiotic stewardship should consider environmental fate of antibiotics. Rosi-Marshall EJ, Kelly JJ. Environ Sci Technol. 49:5257–8, 2015.
- Progress on utilizing hyperthermia for mitigating bacterial infections. Taylor Ibellia, Sarah Templetonb and Nicole Levi-Polyachenkoc. Intern J Hyperth. 34(2):144–156, 2018.
- Influence of tick and mammalian physiological temperatures on Borrelia burgdorferi biofilms. Shaikh S, Timmaraju VA, Torres JP, Socarras KM, Theophilus PAS, Sapi E. Microbiology 162:1984–1995, 2016.
- Evidence Of In Vivo Existence Of Borrelia Biofilm In Borrelial Lymphocytomas. Sapi E, Balasubramanian K, Poruri A, Maghsoudlou JS, Socarras KM, Timmaraju AV, Filush KR, Gupta K, Shaikh S, Theophilus PAS, Luecke DF, MacDonald A, Zelger B. Eur J Microbiol Immunol. 6(1):9–24, 2016.
- Destruction of the outer membrane permeability barrier of Escherichia coli by heat treatment. Tsuchido T, Katsui N, Takeuchi A, et al. Appl Environ Microbiol. 50:298–303, 1985.
- Changes in antibiotic sensitivity and cell surface hydrophobicity in Escherichia coli injured by heating, freezing, drying or gamma radiation. Mackey B. FEMS Microbiol Lett. 20:395–9, 1983.
- Biofilm formation by Borrelia burgdorferi sensu lato. Timmaraju VA, Theophilus PAS, Balasubramanian K , Shakih S, Luecke DF, Sapi E. FEMS Microbiol Lett. 362(15):1-12, 2015.