Recent News 48 : PAS: The Fast PASS to The Future

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PAS: The Fast PASS to The Future


“Two Can Play at That Game” by Ellie Jameson

In recent years, antibiotic resistant bacteria, also referred to as “superbugs,” have become a major threat, adapting to withstand widely used antibiotic treatment. The fast reproduction of bacteria has brought constant mutations, with some mutations making stronger bacteria that survive and reproduce themselves.

Ultimately this natural selection leads to bacteria that are strong enough to survive most antibiotics we have to offer. Bacterial evolution has caught up to human ingenuity and threatens to surpass it. These superbugs threaten to kill up to 10 million people per year by 2050, but antibiotics remain too valuable a resource to entirely replace. The only remaining option is to adapt with the times and develop evolving weaponry and treatment, harnessing man and nature to beat our old enemy.

Bacteriophages are to a bacterium as a tiger is to a lamb. As the natural predator of bacteria, bacteriophages offer both advantages and disadvantages as treatment options compared to antibiotics. The main benefits are that, unlike antibiotics, bacteriophages can adapt to bacterial mutations. Bacteriophages are also easily accessible and found in the wild. Additionally, bacteriophages cannot attack or damage human cells in any way due to the nature of our eukaryotic cells.

However, the problem with bacteriophage-related treatment possibilities is mainly their high specificity. Bacteriophages are highly specialized, and each bacteriophage strain can only hunt down and kill one specific type of bacteria.


Tradeoff in Fitness (Li et Al). Diagram of how phages can cause disorders for bacteria, even if the bacteria evolve against it

Phage-Antibiotic Synergy (PAS), offers the benefits of both mass-producible and inexpensive antibiotics, along with the adaptability and effectiveness of phages. PAS works by forcing the bacteria to multi-task. Multi-tasking compromises quality and performance even in humans, so imagine the damage to the simple bacteria. Adaptations to phages require previous mutations that were rendered moot to be sacrificed.

For example, in P. aeruginosa, the bacteria operate pumps to expel antibiotics. In order to adapt to phages, the pumps must be shut off to conserve energy and resources for the immediate threat.

Another example involves the receptors a bacterium uses: phages are so hyper specific that the bacterium simply needs to mutate these receptors to prevent its death. Yet the bacteria’s receptors are also needed for other functions, such as resource transport and infection, slowing virality and even killing the bacteria in some cases. Even if the phages alone cannot defeat bacteria, the antibiotics come in at the end to deal with weakened bacteria that can only multi-task to increasing detriment.


Diagram of PAS effectiveness, versus lone Phage and Antibiotic Treatments

But what of bacteria and their ever evolving capabilities? Bacteria cannot even adapt to PAS, evolution inherently forces the more immediately beneficial adaptation to go through, rather than playing the long game. As such mutated bacteria only evolve to deal with one opponent, leaving them weak to the second. Adapting to both is slow and just leaves a weaker defense as a whole, and even if successful, the redistributing of the bacteria’s faculties to the task will severely slow the infection and prevent spread.

PAS does suffer from issues however. For example, pairings would have to be done carefully, due to the high specificity of phages and the possibility of phage antagonism, where antibiotics interfere or kill phages. For example certain antibiotics like the Tobramycin class of antibiotics inhibit phage reproduction via its inhibition of ribosome functions. PAS is also affected by the immune system, whilst phages cannot hurt human cells, the immune system can hurt phages. Ironically, in this scenario, the body would weaken itself to the bacteria.

PAS is a novel concept that is still underexplored, but could potentially help end the threat posed by superbugs. By combining the advantages of both medical technologies, it could represent the next step in medicine.

With more research, we might be able to pair the two and develop powerful tools against any superbug.

With genetic engineering on the horizon, we may even be able to engineer phages to target certain bacteria and viruses, overcoming their high specificity and expanding this treatment to a broader range of bacterial infections. PAS offers a promising way forward as bacteria continue to threaten us, and could provide us with a path into a safer future.





References:

Barron, Madeline. “Phage Therapy: Past, Present and Future.” American Society for Microbiology, American Society For Microbiology, 31 Aug. 2022, asm.org/Articles/2022/August/Phage-Therapy-Past,-Present-and-Future. Accessed 8 Mar 2025.
Li, Xianghui, et al. “A Combination Therapy of Phages and Antibiotics: Two Is Better than One.” International Journal of Biological Sciences, vol. 17, no. 13, 18 Aug. 2021, pp. 3573–3582, www.ncbi.nlm.nih.gov/pmc/articles/PMC8416725/, https://doi.org/10.7150/ijbs.60551. Accessed 17 Sept. 2021.
Łusiak-Szelachowska, Marzanna, et al. “Bacteriophages and Antibiotic Interactions in Clinical Practice: What We Have Learned so Far.” Journal of Biomedical Science, vol. 29, no. 1, 30 Mar. 2022, jbiomedsci.biomedcentral.com/articles/10.1186/s12929–022–00806–1, https://doi.org/10.1186/s12929-022-00806-1.
Segall, Anca M, et al. “Stronger Together? Perspectives on Phage-Antibiotic Synergy in Clinical Applications of Phage Therapy.” Current Opinion in Microbiology, vol. 51, no. 51, Oct. 2019, pp. 46–50, https://doi.org/10.1016/j.mib.2019.03.005.

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