Did you know that we can cure infections with viruses? To be more specific, researchers are developing methods of curing bacterial infections with bacteriophages, viruses that infect bacteria. This is called phage therapy. Although phage therapy was discovered a century ago, it was unpopular and less understood compared to antibiotics. Phage therapy recently gained much attention again due to its potential to help us with the current antibiotic resistance crisis.
Biology Background
Bacteriophages, like any other viruses, need a host to survive and reproduce. Bacteriophages only infect bacteria and are harmless to other organisms such as humans. In order for infection to take place, a bacteriophage first binds to a bacterium’s surface receptor and injects its genetic material (DNA or RNA). The bacteriophage uses the cell’s machinery to reproduce, and bacteriophages eventually make their host bacteria lyse.
Bacteriophages tend to be host-specific because infection can only occur when there are specific complementary receptors on the bacterial cell surface. As a result, many strains of bacteriophages can only infect specific species of bacteria. Interestingly, bacteria and bacteriophages have constantly been evolving to outmaneuver each other. For instance, bacteria species often evolve to have altered receptors that can evade infection, while bacteriophages often evolve to be able to use those new receptors.
Phage Therapy: Benefits
The most hopeful point about phage therapy is its potential to kill antibiotic-resistant bacteria. The current antibiotic resistance crisis is identified as a global threat by both the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC). Clinical trials with phage therapy have shown promising results in combating antibiotic-resistant bacteria, and there were also real cases where doctors used phage therapy to save patients from life-threatening infections. Two famous cases of such are the case of Tom Patterson in 2016 and the case of Isabelle Carnell-Holdaway in 2018.
Investigations also suggest that phage therapy can induce multidrug-resistant bacteria, such as Pseudomonas aeruginosa, to become sensitive to antibiotics again. In other words, bacteria that evolve to evade phage therapy may experience an evolutionary trade off to become more responsive to antibiotics. The prospect of bacteria developing resistance against phage therapy would therefore be less concerning, especially since bacteriophages themselves evolve too.
Another big advantage of phage therapy is the host-specificity of bacteriophages. Antibiotics attack a wider range of bacteria, so they often cause secondary damage to bacteria that are beneficial to our body. Since bacteriophages tend to attack specific strains of bacteria, phage therapy could be useful in targeting specific infections without disturbing good bacteria.
Phage Therapy: Limitations
Bacteriophages’ host specificity may also act as a disadvantage. Phage therapy would require identifying the specific bacterial strain that is to be treated and finding the exact bacteriophage that can work. Treatment becomes especially difficult with infections involving multiple strains of bacteria. This is in contrast to antibiotics, which work against a wide range of bacteria.
Phage therapy may also cause adverse immune responses, although more research is needed to confirm this. Studies with mice showed minimal inflammatory responses against bacteriophages, which is not too surprising because bacteriophages are also external viruses from the perspective of the immune system. There are many more uncertainties to address until phage therapy can be widely used, so for now, the idea of phage therapy seems closer to experimental than practical.
More Research On the Way
Studies are gradually advancing our progress with phage therapy. In particular, researchers are actively experimenting with bioengineered phages and phage-derived lytic proteins. Phage therapy, if developed successfully, would be helpful not only for curing humans, but also for curing animals, protecting food from bacterial pathogens, disinfecting hospital surfaces, etc. Hopefully, more research will soon allow phage therapy to become a practical and effective solution to fighting antibiotic-resistant bacteria.
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