The Role of Glutathione in Disrupting Biofilms

Glutathione is a natural antioxidant found in every cell of our bodies. It has many uses within the cell from clearing free radicals to disabling toxins secreted by harmful bacteria. Ongoing research is constantly revealing all the amazing benefits that glutathione is able exert within our bodies. One of the major up-and-coming discoveries is that glutathione is able to disrupt bacteria-made biofilms.

Biofilms

Biofilms are a thin, slimy film of bacteria that are able to adhere to a surface. One of the most commonly known biofilms is dental plaque that forms on the surface of teeth. They are often found in wet or liquid places commonly called pond scum. It is advantageous for bacteria to form biofilms as they give the colony more resistance to external environmental factors such as lack of water and presence of antibiotics.

Biofilm formation is a constant concern in hospitals as it is a major cause of hospital acquired infections (nosocomial infections). When a bacterium finds itself in an appropriate environment, it starts a colony that will form into a biofilm. Some common places these biofilms can be found in a hospital include: implants, catheters, IVs or ventilator tubes. Once a biofilm is formed, it becomes nearly impossible to get rid of, even with the use of heavy antibiotics. Due to the dangers of biofilms in hospitals, constant research is performed to learn how to effectively, and efficiently, remove them.

Cystic Fibrosis

Biofilms not only grow on hospital instruments, but can grow in, and on, living things (such as teeth mentioned earlier). Pseudomonas aeruginosa (Pseudomonas) is one of these bacteria that is known to develop a biofilm within the lungs of patients with Cystic Fibrosis (CF). Pseudomonas is naturally antibiotic resistant on its own, and when it develops a biofilm, it becomes nearly impossible to treat with antibiotics. Therefore, patients who have CF and contract Pseudomonas have a higher chance of morbidity.

Treatment of Pseudomonas for CF patients is very limited and generally the best option is a lung transplant. We are beginning to see glutathione may be a key treatment for CF patients and Pseudomonas.

Pseudomonas and Biofilms

Bacteria grow a biofilm in many ways, however, for now we will focus as to how Pseudomonas makes one. When Pseudomonas finds a place to latch and form a biofilm, it starts to release extracellular DNA. This DNA is used as an anchor to attach itself better on a surface while holding the colony together. When attached, Pseudomonas starts to release pyocyanin, a toxin helping form a stronger biofilm. Pyocyanin can act as an oxidative agent (i.e. a free radical) within the lungs. When pyocyanin is secreted inside a host, such as a CF patient, it can make its way inside the cells of the host and start to cause oxidative stress. This oxidative stress will cause the cells to undergo cellular distress and lead to apoptosis, or programmed cell death (under extreme conditions). Pseudomonas is able to cause such distress in cell since it so hard to remove or stop it.

Not only does pyocyanin create oxidative distress, it completely depletes the intracellular glutathione cells contain. As mentioned earlier, one of the main jobs of glutathione is to remove anything capable of causing oxidative damage; Pseudomonas can excrete enough pyocyanin to overcome the body’s ability to replenish glutathione in time. Consequently, the cell is unable to remove pyocyanin fast enough and becomes overrun with the toxin.

Glutathione and Biofilms

Glutathione has been shown to help remove pyocyanin toxin from inside cells effectively while neutralizing it from inside the biofilm. When excess glutathione is added to a site of biofilm, glutathione is able to neutralize the toxin in addition to disrupting the extracellular DNA holding the biofilm together. This disruption helps the biofilm become susceptible to removal from whatever type of surface it is attached on. Ultimately, at a high enough concentration, glutathione is even able to kill bacteria on its own.

Several studies show when glutathione is used along with antibiotics, it is able to effectively, and synergistically, remove even the most antibiotic resistant Pseudomonas biofilms.

Conclusion

One major factor that has reduced the effects of glutathione products on the market is the reactive nature of glutathione. Glutathione is a highly reactive antioxidant known to react with oxygen in the air. From this reaction, glutathione loses its potency and is unable to exert any antimicrobial properties.

For this reason, VARS Glutathione was created as the first functional glutathione without oxidation for at least one year. The stability of VARS Glutathione by avoiding oxidation makes it more effective than any other glutathione product exposed to oxygen. Try VARS Glutathione today and start feeling the difference today!   

REFERENCES

Alharbe R, Almansour A, Kwon DH. 2017. Antibacterial activity of exogenous glutathione and its synergism on antibiotics sensitize carbapenem-associated multidrug resistant clinical isolates of Acinetobacter baumannii. International Journal of Medical Microbiology 307:409–414.

Aquilano K, Baldelli S, Ciriolo MR. 2014. Glutathione: new roles in redox signaling for an old antioxidant. Frontiers in Pharmacology 5.

Das T, Simone M, Ibugo AI, Witting PK, Manefield M, Manos J. 2017. Glutathione Enhances Antibiotic Efficiency and Effectiveness of DNase I in Disrupting Pseudomonas aeruginosa Biofilms While Also Inhibiting Pyocyanin Activity, Thus Facilitating Restoration of Cell Enzymatic Activity, Confluence and Viability. Frontiers in Microbiology 8.

Dietrich LEP, Teal TK, Price-Whelan A, Newman DK. 2008. Redox-Active Antibiotics Control Gene Expression and Community Behavior in Divergent Bacteria. Science 321:1203–1206.

Giamarellou H. 2006. Treatment options for multidrug-resistant bacteria. Expert Review of Anti-infective Therapy 4:601–618.

He L, He T, Farrar S, Ji L, Liu T, Ma X. 2017. Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species. Cellular Physiology and Biochemistry 44:532–553.

Klare W, Das T, Ibugo A, Buckle E, Manefield M, Manos J. 2016. Glutathione-Disrupted Biofilms of Clinical Pseudomonas aeruginosa Strains Exhibit an Enhanced Antibiotic Effect and a Novel Biofilm Transcriptome. Antimicrobial Agents and Chemotherapy 60:4539–4551.

Muller M, Merrett ND. 2015. Mechanism for glutathione-mediated protection against the Pseudomonas aeruginosa redox toxin, pyocyanin. Chemico-Biological Interactions 232:30–37.

Omalley YQ, Reszka KJ, Spitz DR, Denning GM, Britigan BE. 2004. Pseudomonas aeruginosa pyocyanin directly oxidizes glutathione and decreases its levels in airway epithelial cells. American Journal of Physiology-Lung Cellular and Molecular Physiology 287.

Pal S, Ramu V, Taye N, Mogare DG, Yeware AM, Sarkar D, Reddy DS, Chattopadhyay S, Das A. 2016. GSH Induced Controlled Release of Levofloxacin from a Purpose-Built Prodrug: Luminescence Response for Probing the Drug Release in Escherichia coli and Staphylococcus aureus. Bioconjugate Chemistry 27:2062–2070.

Schairer DO. 2013. Evaluation of the antibiotic properties of glutathione. J Drugs Dermatol12:1272–1277.