Tackling antibiotic resistance using phage therapy

By Shivani Raja

Antibiotics are the current primary treatment for bacterial infection. Increased antibiotic exposure has encouraged the growth of resistant bacterial strains, and hence created a demand for new antibiotic drugs to tackle these strains. Phage therapy, a treatment utilising the antibacterial properties of microscopic viruses called bacteriophages, may be a potential antibiotic alternative.  However, a problem arises as a result of antibiotic overuse, such as in factory farms, where animals are administered large doses of antibiotics to prevent disease (McKenna, 2015). Bacterial strains continually exposed to antibiotic drugs can develop antibiotic-resistant genes evolving into fitter strains. As a result, there is an ongoing demand for new antibiotics to tackle strains resistant to existing ones. Some bacterial strains, such as Methicillin Resistant Staphylococcus Aureus (MRSA), have developed resistance to multiple antibiotic drugs and are deemed superbugs.

Despite the demand for new antibiotics, it can take up to 10 years to locate, develop and test a new drug. During this time, a bacterial culture of just 10 cells will have proliferated into an infinite population with new mutations and characteristics. Following development of a new antibiotic, resistance can be established within days given the rate of bacterial proliferation, rendering these 10 years of production useless (McKenna, 2015).

The time required for antibiotic development, combined with the depleting number of places to search for new drugs, has led to research into phage therapy as a possible alternative. Phage therapy uses viruses called bacteriophages, or phages for short, to treat bacterial infection. The treatment has been around for almost a century, though results from early usage were inconsistent. Following the discovery of antibiotics, research into phage therapy became less popular (Buschman & LaFee, 2017). However, in recent years, phage therapy has regained interest as a treatment for bacterial disease. 

Bacteriophages are the most abundant organism on earth. They are in fact neither dead or alive and depend on a bacterial host for survival. Phage therapy involves injecting a patient with a sample of phages, which locate and destroy pathogenic bacteria. Each phage is a microscopic unit comprising an icosahedron containing the phage’s genetic material, a long tail and fibre legs. Upon interaction with a bacterium, a phage will connect its legs to receptors on the bacteria, squeeze its tail, and submit its genetic information into the bacterium. This prompts new, endolysin-producing phages to reproduce within the bacterial cell causing lysis (Lin, Koskella & Lin, 2017). 

The bacterial specificity of phages means that health-protecting gut flora bacteria are only minimally impacted during phage therapy, as opposed to broad-spectrum antibiotics which destroy these beneficial bacteria. On the other hand, by targeting a single pathogen, phage therapy is potentially less effective against infections colonized by multiple strains of bacteria such as infected burn wounds. One approach to this problem is the use of phage cocktails containing a variety of phages specific to different bacterial strains (Loc-Carrillo & Abedon, 2011).

Phages are widely abundant in sewage and other waste materials and can be administered as liquids, creams, and impregnated into solids (Loc-Carrillo & Abedon, 2011). Another benefit of phage therapy is that there are minimal side effects. Whereas antibiotic usage may have secondary outcomes such as antibiotic-associated diarrhoea, phage therapy  appears to have minimal secondary effects for non-immunocompromised patients. However, patients with weakened immune systems may experience an adverse reaction, which could hypothetically worsen their condition (Lin, Koskella & Lin, 2017).

The use of phage therapy as an antibiotic alternative begs the question of whether bacteria will develop into phage-resistant strains. However, studies have shown that specific antibiotic resistance mechanisms do not translate into mechanisms of phage resistance, and that bacteria cannot be both antibiotic- and phage-resistant at the same time. (Loc-Carrillo & Abedon, 2011). As a result, the use of phage therapy in conjunction with antibiotic drugs may be necessary to address the growing issue of antibiotic-resistant superbugs. 

A few phage treatments have already passed regulatory standards, having been classified by the FDA as GRAS (Generally Regarded As Safe) (Loc-Carrillo & Abedon, 2011). Furthermore, phage therapy has been successfully administered to select patients suffering from bacterial disease, such as Tom Patterson, who was successfully cured of a multi-drug resistant bacterial infection using a cocktail of four phages (Buschman & LaFee, 2017).  

Phage therapy is a promising antibacterial treatment and antibiotic alternative, with many advantages. Following further research and clinical trials, phage therapy may soon become the primary defence against antibiotic-resistant bacterial strains, potentially saving millions of lives from bacterial disease. 

References: 

LaFee, S. & Buschman, H. (2017) Novel Phage Therapy Saves Patient with Multidrug-Resistant Bacterial Infection. Available from: https://health.ucsd.edu/news/releases/pages/2017-04-25-novel-phage-therapy-saves-patient-with-multidrug-resistant-bacterial-infection.aspx [Accessed 26th August 2020]

Lin, D. M., Koskella, B., & Lin, H. C. (2017) Phage therapy: An alternative to antibiotics in the age of multi-drug resistance. World Journal of Gastrointestinal Pharmacology and Therapeutics. 8(3), 162-173. Available from: doi.org/10.4292/wjgpt.v8.i3.162

Loc-Carrillo, C., & Abedon, S. T. (2011) Pros and cons of phage therapy. Bacteriophage. 1(2), 111–114. Available from: doi.org/10.4161/bact.1.2.14590
TED. (2015) Maryn McKenna: What do we do when antibiotics don’t work any more?. [Video] Available from: https://www.youtube.com/watch?v=o3oDpCb7VqI [Accessed 26th August 2020]

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