A Potential Alternative to Antibiotics
By Octavia Marshall
In 2019, an estimated 1.27 million people died directly due to antibiotic resistance. While antibiotic resistance occurs naturally due to random mutations, the overuse and misuse of antibiotics is causing a rise in antibiotic resistance globally, leading to an increasing number of common infections becoming harder to treat. Fortunately, it is possible that phage therapy could provide an alternative treatment, though the evidence of the efficacy of this is limited.
Phage therapy refers to the use of a type of virus called bacteriophages, also referred to as phages, to treat infections. It is surprising, considering the events of the last 2 years, that such an important advancement in medicine could come in the form of a virus. However, viruses are incredibly diverse and bacteriophages are very different from COVID-19; most significantly in that they only infect bacteria. This is because the viruses will only bind to specific host surface molecules, such as membrane proteins, lipids or the carbohydrate moieties on either glycoproteins or glycolipids. The bacterium is destroyed when the phage binds to the cell and inserts its genetic material into the host’s DNA, using the cell machinery to replicate, resulting in lysis (the cell bursts).
The specificity of the receptor proteins of the bacteriophages is what could make phage therapy highly effective because it allows for specific bacteria to be targeted. Most bacteria in our body are actually beneficial to us; it is a symbiotic relationship. Not only do bacteria aid our digestion and help us synthesise vitamins (like vitamin K), but there have been links between depression and an unhealthy microbiome, with a study published in Nature Microbiology showing a correlation between having depression and lacking two groups of bacteria, Coprococcus and Dialister, in the gut. Being able to target only harmful bacteria would remove one of the major downsides of antibiotics by reducing disruption to our gut flora (see further reading for more information).
Phages have successfully been used in clinical trials in a number of medical disciplines and 59 studies have shown improvement in 79% of patients treated with phage therapy. However, despite this figure being very promising, many of these cases involved the use of phages along with other treatments, meaning that the actual impact of phage use could be lower than suggested. Furthermore, the immune response to phages could diminish the benefits of the treatment, though evidence on this is limited and more research is needed to determine its impact, particularly to see whether anti-phage antibodies could make repeated treatments less effective. There is also the original problem of resistance, which is why a mix of different phages are used and often tailored to the patient. This could present an issue in the widespread use of phages as a more general mix would be used and the prevalence of resistant bacteria could increase as competition from non-resistant strains is lessened, so it must be carefully monitored.
While phage therapy has been in use since the 1920s, it has only recently started to gain popularity due to the challenge of antibiotic resistance. The main limitation of phage therapy is that there haven’t been enough studies or the sample sizes of existing studies haven’t been large enough to provide conclusive evidence of the efficacy of the treatment and it isn’t known what the best dosage or method of administration is. However, it is considered safe due to the phages’ inability to infect eukaryotic cells and could provide a solution to the rise in superbugs due to antibiotic resistance in the near future, provided that more research is carried out.
Sources/ further reading:
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext
https://www.nature.com/articles/d41586-019-00483-5
Facing a new challenge: the adverse effects of antibiotics on gut microbiota and host immunity
Anti-phage serum antibody responses and the outcome of phage therapy
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070868/
For more of an explanation on bacteriophages: https://www.khanacademy.org/science/biology/biology-of-viruses/virus-biology/a/bacteriophages