Could bacteriophages offer a solution to the increase in antibiotic resistance?

Ben – Year 12 Student

Editor’s Note: Aspiring medic and Oxbridge applicant Ben, now in Year 13, writes here for the school Science Magazine on whether or not bacteriophages offer a viable solution to the concerning increase observed in antibiotic resistance. This is Ben’s first publication in The GSAL Journal. CPD

Featured image: Phage injecting its genome into bacterial cell. (Creative Commons)


Bacteriophages, sometimes referred to as ‘phage’, are viruses that solely infect bacteria. They do so by injecting their genetic material, stored as nucleic acid in a part of the bacteriophage called the capsid, into the bacterium where it then takes over the bacterial cell and utilises it to synthesise the components needed to make more bacteriophages. The new bacteriophage particles most commonly then assemble inside the bacterial cell and burst out of the cell in a process known as lysis. Bacteriophages which carry out lysis are referred to as ‘lytic phages’. During lysis, two proteins, lysin and holin, are used to break apart the cell wall of the bacterial cell, releasing the new bacteriophage particles and killing the bacterium in the process. 

How can bacteriophages be used as an alternative to antibiotics?

In principle, all antibiotics work by interfering with processes that are necessary for the bacteria to stay alive, reproduce, or both, whilst not interfering with the way human cells function. As a result, antibiotics can be used to treat a bacterial infection as they kill bacteria whilst leaving human cells unharmed. Many antibiotics can also be used to treat a wide array of infections due to the processes that antibiotics interfere with in bacteria being similar between species. Bacteriophages can be used in essentially the same way; they only infect and kill bacterial cells and can therefore be used to treat a bacterial infection whilst leaving human cells unharmed. However, whilst antibiotics tend to be useful in treating a wide range of bacterial infections, bacteriophages are incredibly specialised and most are only able to infect a subset of a bacterial species due to the evolution of both bacteria and bacteriophages.

Due to bacteriophages being so specialised, it is more difficult to use them as a treatment for a bacterial infection than antibiotics. The first step taken in treating somebody with a bacterial infection using bacteriophage therapy is to accurately identify the bacterium causing the infection and then to select a bacteriophage which is known to infect that specific bacterium. Not a lot of research has yet been conducted into identifying which bacteriophages infect which bacteria and as a result often it is not known which bacteriophage would be effective against a particular bacterium; therefore, it is necessary to conduct a search to identify a suitable bacteriophage. This all takes time and the bacterial infection may have become life threatening by the time a suitable bacteriophage is identified, if one is found at all. More research into the uses of bacteriophages would be required to make them viable as an alternative to antibiotics. However, there is a great necessity to find alternatives to antibiotics as bacteria are rapidly becoming resistant to antibiotics due to their widespread use and this is considered by many experts to be one of the greatest threats to public health; the CDC estimates that in 2013, 1.15% of people who caught antibiotic resistant bacterial infections in North America died, and by 2019 this figure increased to 1.25%. Many bacteria are now resistant to multiple antibiotics, making them extremely dangerous. In order to combat antibiotic resistant bacterial infections it is necessary to develop alternatives to antibiotics, especially when considering that it takes ten years on average for new antibiotics to be developed and introduced – and they are rapidly becoming less effective.

The reason why bacteriophages seem to have the potential to be a promising alternative to antibiotics is that whilst bacteria can develop resistance to bacteriophages through evolution, bacteriophages can also evolve in order to become more efficient at infecting bacteria. Studies into whether a bacterial species could conceivably become resistant to all bacteriophages which infect that particular species have thus far concluded that it seems to be highly unlikely due to the fact that bacteriophages can adapt to overcome bacterial resistance to bacteriophages. Furthermore, there is research to suggest that in order to become resistant to bacteriophages, bacteria need to make significant changes to their structure, which can result in the bacteria no longer being resistant to antibiotics, or can lead to the bacterium no longer being able to harm its host. As a result of this, the use of bacteriophages as an alternative to antibiotics could lead to antibiotics becoming a viable method of treatment for specific bacterial infections again. The changes that bacteria need to make to become resistant to bacteriophages can also have potential detrimental impacts on the bacteria’s ability to thrive in its environment, meaning that it can actually be undesirable for a bacterium to become resistant to bacteriophages at all.

Examples of bacteriophage therapy being used to treat antibiotic resistant bacterial infections

Bacteriophage therapy is currently in the early stages of development as a treatment option and is only recently being approved by government organisations; the FDA approved clinical trials for bacteriophage therapy in February 2019. In terms of individual cases of people being treated with bacteriophage therapy, in May 2019 a teenager with cystic fibrosis and a multi-drug resistant Mycobacterium abscessus bacterial infection was given a cocktail of genetically engineered bacteriophages by an international team of researchers and clinicians led by Graham Hatfull at the University of Pittsburgh. The patient was completely cured of the infection. In a similar case, a man named Tom Patterson caught a multi-drug resistant Acinebacter baumannii and was near total organ failure when he was given bacteriophage therapy. He was given a bacteriophage cocktail daily, intravenously and also through a catheter into his abdomen, for two months, and was completely cleared of the infection within three months. Both of these cases illustrate that bacteriophages seem to be a practical and effective alternative to antibiotics and highlight the potential utility for bacteriophage therapy to be used when the infections in need of treatment are resistant to many types of antibiotics. With regards to clinical trials, Armatapharma is an American pharmaceutical company currently conducting a stage one clinical trial for a therapeutic cocktail of three bacteriophages used to treat infections caused by the bacterium Staphylococcus aureus, and are in the preclinical stage for a bacteriophage treatment for infections caused by Pseudomonas aeruginosa, both of which are bacteria which are often resistant to antibiotics. Armatapharma is only one of an increasing number of companies now exploring the potential of bacteriophage therapy through clinical trials, which makes the prospect of bacteriophages becoming a realistic alternative treatment method to antibiotics a tangible outcome.

References

https://www.phagetherapycenter.com/pii/PatientServlet?command=static_phagetherapy&secnavpos=1&language=0  Accessed 11/11/19

https://journals.lww.com/jwocnonline/pages/results.aspx?txtKeywords=bacteriophages Accessed 17/11/19

https://onlinelibrary.wiley.com/doi/full/10.1111/j.1749-4486.2009.01973.x Accessed 17/11/19

https://www.thoughtco.com/facts-about-bacteriophages-373885 Accessed 17/11/19

https://www.ncbi.nlm.nih.gov/pubmed/1406491 Accessed 17/11/19

https://www.ncbi.nlm.nih.gov/books/NBK21417/ Accessed 17/11/19

https://www.phagetherapycenter.com/pii/PatientServlet?command=static_phagetherapy&secnavpos=1&language=0 Accessed 17/11/19

https://www.nature.com/scitable/definition/bacteriophage-phage-293/ Accessed 17/11/19

https://learn.genetics.utah.edu/content/microbiome/antibiotics/ Accessed 17/11/19

https://www.cdc.gov/drugresistance/biggest-threats.html Accessed 17/11/19

http://sitn.hms.harvard.edu/flash/2018/bacteriophage-solution-antibiotics-problem/ Accessed 17/11/19

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694056/ Accessed 17/11/19

https://www.nature.com/articles/s41587-019-0133-z Accessed 17/11/19

https://www.armatapharma.com/pipeline/pipeline-overview/ Accessed 17/11/19

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694056/#R23 Accessed 17/11/19

Ben 095242

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