What are Phages? – A look into their history and applications
The x174 and M13 are with a very different structure. Aqsens Health uses both phages in biosensors applications.
You might have seen the word ‘phage’ or ‘bacteriophage’ appear more often in the media, new articles, and scientific publications in recent years. But what exactly are bacteriophages? What do they do, and how can they be used in health care? This blog seeks to answer a few of those questions.
What are bacteriophages?
Bacteriophages, or phages for short, are the most numerous microorganisms on the planet. Some estimate that the number of phage particles on Earth is 10 to the power of 31 – a “nonillion”, which roughly translates to around a trillion phages for every grain of sand in the world.
Bacteriophages have a crucial role in regulating the world’s bacterial populations. Some studies estimate that they kill anywhere between 15–40% of the bacteria in our oceans every day. Phages are virus-like organisms that are present everywhere – in water, soil, plants and even our skin and metabolism. They can survive in very extreme environments and withstand very high or very low temperatures.
The discovery of phages
Bacteriophages were first discovered and used successfully in treatment already in the beginning of the 20th century. William Twort first observed them in 1915, after which Felix d'Herelle realized their bacteria-killing potential in 1917.
However, the research and development of bacteriophages was quickly overshadowed by the discovery of penicillin. While antibiotics reliably killed all bacteria making their administration extremely easy, the use and research into phages, which required significantly more skill and knowledge, declined significantly. For several decades phages were left on the back burner as antibiotics seemed to be the ultimate solution to all infections.
But luckily, the study of phages did not die out completely. Their study and development continued throughout the 20th century in a few places around the world.
How phages operate
Because there is an indescribable number of phages on the planet, there are also several thousand different types of phages that greatly vary in size, appearance and in the number of genomes they carry. For example, the phages Aqsens uses in research, the x174 and M13 phage, look extremely different. However, there is something in common between all phages. All phages are viruses made up of proteins that surround and protect their genetic material, which is either DNA or RNA.
Since bacteriophages are a type of virus, like other viruses they do not have the ability to replicate on their own. To reproduce, they need a host cell. And bacteriophages are very specific about their host cell. Through millions of years phages have evolved and specialized to survive by exclusively infecting and killing bacterial cells without harming the surrounding human or animal cells. But the phage’s specificity does not end there – specific phages are programmed to only kill specific species of bacteria, like predators only hunting one type of prey. This is referred to as the phage’s affinity towards their targets.
When phages find their bacterial host cell they attach to it and start using the host cell’s nutrients to multiply and replicate themselves inside the host. And when all the nutrients in the host cell are used, the new phages make their exit. The new phages produce an enzyme called endolysin that destroys the host bacteria’s walls, killing the host from the inside and releasing the new phages. Then, the newly released phages start to look for their own host cell to infect, and the process starts again from the beginning.
Phages could be the answer to the growing need for alternative solutions
In the last few decades antibiotic-resistant bacteria have become an ever more serious global threat. Some researchers and scientists have even proclaimed the era of antibiotics to be over as doctors and hospitals struggle with new forms of bacteria that cannot be defeated with conventional means. According to WHO, antibiotic resistance is one of the biggest threats in health care globally. It’s estimated that at least 700,000 people die annually because of drug-resistant diseases, and the number will continue to rise if no action is taken. This is where phages come in.
Through the years phages have been sporadically used around the world to treat individual patients battling with antibiotic resistant bacterial infections, often with success. This success is due to the high evolvability of phages, and their ability to ignore the resistance bacterias develop towards antibiotics. In addition to therapeutic use, phages also have other potential applications in screening and diagnostics and they have already been successfully used as a part of diagnostic processes.
The phages’ ability to evolve is so vast that humans will never be able to discover all of their different possibilities this ability generates. They play a crucial role in developing innovative solutions to many problems healthcare faces, and it is no surprise that the interest in phages has picked up significantly during the last 20 years. The next big discoveries are most likely just around the corner.
Sources:
Keen EC. A century of phage research: bacteriophages and the shaping of modern biology. Bioessays. 2015;37(1):6-9. doi:10.1002/bies.201400152
Clokie MR, Millard AD, Letarov AV, Heaphy S. Phages in nature. Bacteriophage. 2011;1(1):31-45. doi:10.4161/bact.1.1.14942
Fernando L. Gordillo Altamirano, Jeremy J. Barr. Phage Therapy in the Postantibiotic Era. Clinical Microbiology Reviews. 2019; 32 (2). doi: 10.1128/CMR.00066-18
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