In this article we will introduce you to bacteriophages (also referred to as phages), what rule do they play in our lives and most importantly, what role they may play in our future.
What is a Bacteriophage?
Bacteriophage, also known as phage is a virus that attacks and destroys bacteria. Bacteriophages do not target bacteria in general. Each phage targets a specific type of bacterium, whilst ignoring the rest.
History of Bacteriophages
Bacteriophages, although only coming into light quite recently, have actually been around for longer than we have. One of the biggest upsides to phage therapy is that it has no side effects to the patients. Bacteriophages do not attack any other bacteria except a specific type or group and our bodies are used to them, as we are surrounded by them. Research has led us in discovering that bacteriophages originate to the early Precambrian Era (the earliest era of Earth’s history, that span across approximately 4.5 billion years ago).
Phages are found everywhere; water, air, soil and practically anywhere and everywhere bacteria can be found. Some go so far as to say that it is because of the presence and the unique functions of bacteriophages, that our environment has not been fully occupied by bacteria. They believe that bacteriophages are organisms that have allowed to control the levels of bacteria in nature.
The discovery of Bacteriophages
Back in 1896, Ernest Hanbury Hankin, an English bacteriologist and aeronautical theorist and naturalist, made a report on the Ganges and Yamuna rivers in India. He stated that the waters seemed to have some sort of antibacterial properties that helped against cholera. In 1915, Fredrick Twort, a British bacteriologist, had also discovered an agent that killed bacteria, however his research had been cut short due to World War I. In 1917, Félix d’Hérelle, a French-Canadian microbiologist, who at the time was working at the Pasteur Institute in Paris, made an announcement of his discovery of “an invisible, antagonistic microbe of the dysentery bacillus”. Félix d’Hérelle gave this organism the name bacteriophage or bacteria-eater that we use today. This name derives from the Greek word phagein, meaning to devour. It is Félix d’Hérelle’s work with bacteriophages that have set the basis for what we know today as phage therapy.
The foundation of Bacteriophage research and institutions
In 1922, Félix d’Hérelle published what became his fundamental work “The Bacteriophage”. This publication attracted many commercial companies who were interested in commercial production of phages. One of the first and prominent companies was the French Harmless Hair Dye Company which was founded in 1909 by Eugène Schueller, a young chemist. This company is known today as L’Oréal.
In 1923, Félix d’Hérelle and a Georgian microbiologist, George Eliava worked together to build the foundation of what we know today as the George Eliava Institute of Bacteriophage, Microbiology and Virology (EIBMV) in Tbilisi, Georgia. In 1937, George Eliava was arrested and executed by Stalin’s communist regime, which made Félix d’Hérelle to never again return to Georgia.
Types of Bacteriophages
There are over 1031 phages on our planet, which makes the bacteriophage population larger than the population of all organisms, including bacteria put together. Bacteriophages split into 2 main types; virulent and temperate phages.
Virulent bacteriophages use the lytic cycle for replication. A phage seeks its target and when found, plants itself on top of the bacterium and injects its nucleic acid inside the host. This allowed for the replication produce to begin. This intensive replication process results in the bacterium to burst open, releasing newly developed bacteriophages to repeat the process.
Temperate bacteriophages use the lysogen cycle for replication. This cycle allows a phage to place its genome into the bacterium but instead of rapid replication, the genome, referred to as a prophage, remains in a dormant state. The prophage either integrate itself to be part of the host’s chromosome or may remain as a plasmid in the cell.
Bacteriophages and antibiotics
Many seem to view phage therapy as an alternative to antibiotic treatments. In truth, both therapies have very different approaches and results and in some cases are used in combination to gain the best possible result. One main difference between the two is that antibiotics are chemically based, whilst bacteriophages are biological. The second major difference is that antibiotics work on all bacteria, including the good bacteria, whilst bacteriophages target specific bacteria.
Antibiotic dosage intake is crucial as to maintain a certain dosage of an antibiotic to be able to give the effect against an infection. Bacteriophages are not so heavily dependent on dosage as their efficiency depends on delivery. Since bacteriophages replicate at a rapid rate, it is important for phages to reach the infection area and begin their replication process. Bacteriophages also face the battle of the bacteria replicating at a fast rate too, that is way phage treatment has patients taking several vials of bacteriophages, to maintain the balance of phages in the system over the number of bacteria.
Bacteria have methods which are implemented when they face bacteriophages, in order to survive. Although such methods are complex, in short, they begin to adjust to become unrecognizable to the phages. Bacteriophages also adjust to the changes that bacteria make to become undetectable to them. In this brief period before that happens, the bacteria become vulnerable to antibiotics.
During the process by which the bacteria must make certain changes to no longer be recognized by the phage, it must let go of their biofilm which covers them and makes them resistant to antibiotics. It is in such cases when a combined treatment using bacteriophages and antibiotics is introduced. Whilst bacteria adjust to become unrecognizable to the phages, they lose their biofilm which leaves them vulnerable to the antibiotics.
Currently only the Eliava Institute in Tbilisi, Georgia has maintained the phage therapy open to patients. For the past several years the topic of using phages for patients openly, has been an open case. However for the time begin, only individuals and research facilities have been working with phages.
There are many issues currently listed which officials must tick off before opening phage therapy to the public. In the EU and US, one of the main concerns is the lack of research. The second main point is that pharmaceutical companies are unable to patent a phage. This is a hold back on the process of producing phages commercially. The full list of issues that need to be address can be found here.
Bacteriophage.news is a virtual space to collect and share information and resources surrounding bacteriophages. This is an introduction to the world of bacteriophages and phage therapy. The information on this site is mainly concentrated on the experiences of patients that have undergone phage therapy, as well as news and research articles of those who work with bacteriophages and developments in this field.