As if I were mining for gold, I had been digging and scraping soil samples from different locations within Auckland. With each sample I had collected, I sensed hope; that I would perhaps find gold. Bacteriophages (phages) are like specs of gold found in dirt, they hold potential powers that could be the answer to many bacterial diseases.
Image 1. Both gold and bacteriophages show similarities in its origins in the soil and value.
Who knew that phages could be found almost everywhere on Earth? They are found ranging from soil, sewage, the depths of oceans to the food we eat (3). Phages are viruses that are abundant in the biosphere with an estimation of 10^32 phages (7). It is often the case that when something becomes abundant, the value drops. But that is not the case here. Several university education programs such as the ‘Science Education Alliance-Phage Hunters Advancing Genomics and Evolutionary Science’ (SEA-PHAGES) are located across the globe. Students participating in these programs such as myself cannot get enough phages. There is a lot we do not know about phages. Currently, 13,074 phages have been found worldwide and counting according to (5), which is comparable to a grain of sand within a desert. The more phages found, the better as we can add to the existing databases of sequenced phage DNA and increase our understanding.
Phages are in fact an old discovery. They were first found in 1915 by Edward Twort and later 1917 by Felix d’Herelle (10). Phages, a strange looking organism as pictured in (Image 2) that resembles a spider. They are specific in that they only target specific strains of bacteria, whilst being ineffective towards mammalian cells (7). Phages infect bacteria by inserting DNA or RNA that incorporates into the bacterium and undergoes either lysogenic cycle or lytic cycle (3). The lysogenic cycle is when genetic material is integrated within the bacterial DNA, and remains dormant, allowing bacteria to replicate normally until it is triggered by an environmental factor, switching it to a lytic cycle. The lytic cycle is when the phage genetic material is replicated by mechanism in bacteria, synthesizing new phages, that build up inside the cell walls of a bacteria until it bursts open (lyses), killing the bacteria (3).
Image 2. A bacteriophage resembling the shape of a spider.
By the 1940s, phages were outshone by chemical antibiotics which emerged. Antibiotics have same superpowers as phages by destructing bacteria, however, they work differently. Instead of lysing bacteria, they can destroy the cell wall or inhibit bacteria to synthesize proteins for growth (6).
Antibiotics, like an ageing old man, grew weaker and weaker. Even a walking stick cannot aid this old man. He could not handle the younger and more active bacteria that adapted faster and increased their resistance. Antibiotic resistance rose rapidly, especially with misuse and over-prescription of antibiotics (1).
We have come to a point where modern medicine is no longer effective. This problem worsened as fewer pharmaceutical companies are manufacturing new antibiotics. Luckily, an alternative exists called phage therapy, one of the strategies implemented the Department of Health (2). Once again, phages were rediscovered.
This comes back to the reason to why I and several other students in 246.202, a class in Massey University may have been out collecting soil. Be it at the crack of dawn or in the thick of the night. At random locations, such as the urban forests, parks, or sidewalk where other passersby would probably question if collecting soil was a weird hobby of mine. It has been a difficult journey so far, with many failed attempts to find a phage, totaling up to 20 soil samples and many other repetitive procedures in the laboratory. Currently, I am up to the stage of characterizing my phage, all derived from a singular pinprick plaque (a clearing on an agar plate due to bacterial lysis) I had found in my 19th soil sample.
The future of phages looked promising to me. Phage therapy so far has been proven successful, having already treated a few diseases before antibiotics (3). They are natural and not chemically harmful such as antibiotics. They are safe towards humans as they specificity targeted bacterial cells. Due to the specificity, they also did not target the good bacteria in your body, unlike antibiotics (6).
Until I heard a question in class; could bacteria could become resistant to phages? I started to question all our efforts of phage hunting. What was the point of finding phages, if the same outcome of resistance were to occur? I wonder if these minuscule things found in soil really is the answer? I have primed myself into seeing phages as gold from the beginning, thinking that resistance would not be possible. However, phage resistance is a possibility. It arises differently from antibiotic resistance, from the incapability of detecting the bacterial antigen (a molecule found on the surface of the bacteria). A mutation on a bacterial antigen will mean that phages cannot attach onto and infect its host (4). Another way a phage becomes resistance is the bacteria’s natural mechanism to cut foreign DNA with enzymes (4). This causes a phage to be resistant to that bacteria it used to be able to infect. While converting to another phage that targets the same bacteria, or a cocktail of phages (use of multiple phages) could be hopeful. This could also fail yet again if no phages or if one phage in the phage cocktail is effective (4). If it were hopeful, new phages would need to be continuously found to make these cocktails, and additionally have ideal characteristics such as fast infection and lysis producing numerous phages (4). It seems like a cycle of needing more phages. It comes down to an ongoing search to isolate more phages that infect the same bacteria in case of phage resistance, which for now is at low risk in comparison to antibiotics.
For now, digging for more soil may be the way to go. Alchemy has not reversed its magic. Gold is still gold. However, not pure gold as it seems.
(1) Antibiotic resistance. (2015). Retrieved from http://www.who.int/en/news-room/fact-sheets/detail/antibiotic-resistance
(2) Henein, A. (2013). What are the limitations on the wider therapeutic use of phage? Bacteriophage, 3(2), e24872. https://doi.org/10.4161/bact.24872
(3) Kutter, E., Guram, G., Alavidze, Z., & Brewster, E. (2013). Chapter 8: Phage therapy.In Grassberger, M., Sherman, R.A., Gileva, O.S., Kim, C.M.H., & Mumcuoglu, K.Y (Eds.). Biotherapy – history, principles and practice: a practical guide to the diagnosis and treatment of disease using living organisms (pp. 191-231). Dordrecht, Netherlands: Springer Netherlands.
(4) Nilsson, A. S. (2014). Phage therapy-constraints and possibilities. Upsala Journal of Medical Sciences, 119(2), 192-198. https://doi.org/10.3109/03009734.2014.902878
(5) The actinobacteriophage database. (n.d). Retrieved from
(6) Trimarchi, M. (n.d.). How do antibiotics work? Retrieved from https://health.howstuffworks.com/medicine/medication/question88.htm
(7) Wittebole, X., Roock, S. D., & Opal, S. M. (2014). A historical overview of bacteriophage therapy as an alternative to antibiotics for the treatment of bacterial pathogens. Virulence, 5(1), 226-235. https://doi.org/10.4161/viru.25991
(Images 1) Smarter hobby. (n.d.). Gold nuggests [Photograph]. Retrieved from
(Images 2) Usagi no Nedoko Kyoto. (n.d.). Enterobacteria phage T4 [Photograph]. Retrieved from https://usaginonedoko.online/products/enterobacteria-phage-t4