Authored by Saahil Joshi
Art by Nabiha Zaman
Bacteriophages, viruses that parasitize and replicate within bacteria, have been emerging as a new type of medical drugs known as phage therapies [1]. Phage therapy presents higher efficacy and fewer side effects than antibiotics, including being impervious to antibiotic resistance and demonstrating significant success in treating strep throat, urinary tract infections, and certain skin infections [2] Treatments such as MRSA, a potentially revolutionary drug for strep throat, and Sb-1, a drug for diabetic toe ulcers, are showing promising success in early trials. Understanding the future of this drug in the clinical environment is key for its success in the next decade.
Phage therapy isn’t exactly novel. 100 years ago, phage therapy was thought to cure cholera and typhoid fever, but this advent didn’t last for long [3]. Likely due to issues regarding bacteria preservation and medical preparations, phage therapy did not see the perceived success that previous research had predicted [4]. As a result, phage therapy descended while the development of standard drugs (i.e. drugs developed today) progressed [5].
Due to the rise of antimicrobial resistance in standard drugs, phage therapy has seen a resurgence. Phage therapies are incredibly specific in their targeting of bacteria, and can be administered topically or systemically [6]. Most common phage therapy treatments are in the context of bacterial resistance that neutralize standard drugs as well as bacterial infections [7]. Because phage therapies only attack bacteria, they are practically harmless to natural human tissue, though they significantly alter the microbial environment [8]. This attribute reduces side effects that standard drugs possess, making them an incredibly useful method of action for infections.
Despite its potential, phage therapy possesses many challenges. Phage therapy is relatively novel, so the full side effects are not fully understood. Although phage therapies specifically target bacteria, they require a great amount of detailed genetic engineering for maximum efficacy, complicating the drug development framework. Furthermore, phage resistant bacteria still remain a concern and due to their novelty, safety studies are required to fully understand how effective phage therapies will be.
Regarding its future in the clinical scene, phage therapy continues to look promising, though standardization and appropriate dosage protocols must be instated to ensure efficacy. Although phage therapies do not possess risks of antibiotic resistance or alike malignancies, side effects are not exactly harmless. Compromises in the immune system that lead to further ailments have been noted in numerous case reports presenting diabetic toe ulcers, which currently stands as a major roadblock in the implementation of phage therapies in the clinical landscape [9]. Some researchers suggest that patients with immunocompromised diseases may not see significant efficacy due to physiological factors dealing with the interplay of the microbial environment and phage therapy [10]. Moreover, phage therapies may have significantly detrimental effects in cancer patients due to their interplay with the tumor microenvironment.
Overall, after a brief analysis of the past, present, and future of phage therapy, bacteriophages remain a very powerful tool for infections and bacterial diseases. They possess properties that make it nearly immune to resistance and highly specific add a level of guarantee to phage therapy. However, phage resistance still remains a concern and due to its specificity, its development requires many more studies to understand its potential. In conclusion, the promise of phage therapy is undeniable and after safety studies and microbiology innovation, phage therapies could very well be a new revolution in the therapeutic landscape.
Works Cited
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Nasser, A., Azizian, R., Tabasi, M., Khezerloo, J. K., Heravi, F. S., Kalani, M. T., Sadeghifard, N., Amini, R., Pakzad, I., Radmanesh, A., & Jalilian, F. A. (2019). Specification of Bacteriophage Isolated Against Clinical Methicillin-Resistant Staphylococcus Aureus. Osong public health and research perspectives, 10(1), 20–24. https://doi.org/10.24171/j.phrp.2019.10.1.05
Liu, D., Van Belleghem, J. D., de Vries, C. R., Burgener, E., Chen, Q., Manasherob, R., Aronson, J. R., Amanatullah, D. F., Tamma, P. D., & Suh, G. A. (2021). The Safety and Toxicity of Phage Therapy: A Review of Animal and Clinical Studies. Viruses, 13(7), 1268. https://doi.org/10.3390/v13071268
Hatfull, G. F., Dedrick, R. M., & Schooley, R. T. (2022). Phage Therapy for Antibiotic-Resistant Bacterial Infections. Annual review of medicine, 73, 197–211. https://doi.org/10.1146/annurev-med-080219-122208
Gordillo Altamirano, F. L., & Barr, J. J. (2019). Phage Therapy in the Postantibiotic Era. Clinical microbiology reviews, 32(2), e00066-18. https://doi.org/10.1128/CMR.00066-18
Monteiro, R., Pires, D. P., Costa, A. R., & Azeredo, J. (2019). Phage Therapy: Going Temperate?. Trends in microbiology, 27(4), 368–378. https://doi.org/10.1016/j.tim.2018.10.008
Uyttebroek, S., Chen, B., Onsea, J., Ruythooren, F., Debaveye, Y., Devolder, D., Spriet, I., Depypere, M., Wagemans, J., Lavigne, R., Pirnay, J. P., Merabishvili, M., De Munter, P., Peetermans, W. E., Dupont, L., Van Gerven, L., & Metsemakers, W. J. (2022). Safety and efficacy of phage therapy in difficult-to-treat infections: a systematic review. The Lancet. Infectious diseases, 22(8), e208–e220. https://doi.org/10.1016/S1473-3099(21)00612-5
Luong, T., Salabarria, A. C., & Roach, D. R. (2020). Phage Therapy in the Resistance Era: Where Do We Stand and Where Are We Going?. Clinical therapeutics, 42(9), 1659–1680. https://doi.org/10.1016/j.clinthera.2020.07.014
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