Written By: Samuel Go

Phage therapy is a method of treating bacterial infections by using bacteriophages, which are viruses that specifically target and kill bacteria from certain strains or species. It is a promising new field of antibacterial treatments because it doesn’t face the problem of bacterial resistance to treatment that antibiotics, or bacteria-killing drugs, do. Phage therapy also doesn’t harm probiotics, or bacteria helpful to the body, unlike some stronger antibiotics. However, it isn’t very accessible or prevalent in most of the world because of a relative lack of clinical trials and lack of precise clinical knowledge as a result. This field of medicine has a lot of room to expand, though. The first bacteriophage clinical trials, which treated against Staphylococcus bacterial infections, started earlier this year in March. The results from those trials will help fill many of the knowledge gaps that exist in the field currently. 

What are the applications for phage therapy?

Researchers are currently developing phage therapy to treat “superbug” infections caused by antibiotic-resistant bacteria. The first pure bacteriophage samples were first extracted from the environment in 1915. The Soviets used phages to treat bacterial infections for decades due to their lack of access to antibiotics. Phages can be used to treat infected wounds, burns, ulcers, and prevent bacterial sepsis, which is the body’s extreme immune response to a bacterial infection.

How does phage therapy work? How is it different from antibiotic therapy?

Bacteriophages infect bacteria by attaching themselves onto bacterial cell membranes, where the bacteria absorb them through endocytosis. Phages then kill their host bacteria by replicating thousands of virus particles and bursting out of the cell. This is quite different from how antibiotics kill bacteria. Antibiotics inhibit either bacterial DNA replication, cell wall production, RNA synthesis, or protein synthesis, which kills the bacterium by permanently shutting down its biological processes, unlike how bacteriophages explode the bacterium from the inside.

Why use phage therapy over antibiotics? 

Phage therapy does not have the problem of eventual bacterial resistance that antibiotic drugs have because viruses are able to evolve to counter bacterial defenses just as fast as bacteria evolve to acquire those same mechanisms. That potentially means that development costs for bacterial infection treatments will go down as pharmaceutical companies no longer need to spend more on discovering new antibiotics to replace ones that bacteria have developed resistance towards. Phage therapy may also weaken bacterial resistance to antibiotics. A study published on Applied and Environmental Microbiology showed that M13 bacteriophages, those that targeted E. coli bacteria, transferred their genes into bacterial genomes and weakened the bacteria, making them less resistant to antibiotic drugs.

Why isn’t phage therapy more common?

Clinical usage of phage therapy has only taken off in Russia, Poland, and Georgia, remaining relatively uncommon everywhere else for a couple of reasons. Clinical trials for phage therapy in the US have only just started this year, mainly because there wasn’t much need for alternatives to antibiotics until now, but also because research on how bacteria eliminate phages wasn’t prevalent until recently. Antibiotic therapy is also more accessible and still seen as safer than phage therapy overall. By far the largest problem with phage therapy is the specificity of care, though. Since most bacteriophages can only target a select group of bacteria, mass production of many different phages for many different bacterial diseases would destroy economies of scale and greatly reduce the economic efficiency of phage therapy as a result. Antibiotics, which generally target a broad range of bacteria, don’t face the economic inefficiency that phages do, which is why they are more common outside of Eastern Europe.

Figure 1

A diagram depicting transduction, or the process by which bacteriophages spread genetic information from one bacterium to another. Genes for resistance to antibiotics and bacteriophages can be spread through transduction.

Source: byjus.com 

Conclusion

Phage therapy is a promising new field in antibacterial treatments with tremendous potential. It is already in widespread use in Eastern European countries like Russia and Georgia and is starting to receive a lot of attention in the West. Although it is economically inefficient and largely untested in the West compared to antibiotics, they could serve as a very valuable asset to leverage against the growing worldwide problem of antibiotic resistance.

References and Sources

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Edgar, R., Friedman, N., Molshanski-Mor, S., & Qimron, U. (2012). Reversing bacterial resistance to antibiotics by phage-mediated delivery of dominant sensitive genes. Applied and environmental microbiology, 78(3), 744–751. https://doi.org/10.1128/AEM.05741-11. 

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Jonathan Anomaly, The Future of Phage: Ethical Challenges of Using Phage Therapy to Treat Bacterial Infections, Public Health Ethics, Volume 13, Issue 1, April 2020, Pages 82–88, https://doi.org/10.1093/phe/phaa003. 

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U.S. Department of Health and Human Services. (2021, March 11). NIH awards grants to support bacteriophage therapy research. National Institutes of Health. Retrieved November 24, 2021, from https://www.nih.gov/news-events/news-releases/nih-awards-grants-support-bacteriophage-therapy-research.