Contents
What is phage therapy?
Bacteriophages, or phages, are viruses that attack bacteria and cause the destruction of the bacterial cell. Viruses are a class of microorganisms. They are alive only when they are present inside a living host. Outside the host cells, they are not alive. They have a very basic structure; the viruses do not have an elaborate cellular structure or functioning. They consist of an outer protein capsid; this protein capsid encases the genetic material, either a deoxyribonucleic acid (DNA) or a ribonucleic acid (RNA), and a tail.
The viral protein coat identifies certain receptors on the surface of the bacterial cell and attaches to it. Then the viral genome is inserted into the bacterial cell and the protein coat gets disintegrated. Then the DNA or RNA integrates itself with the genome of the host cell. After that it takes control of the host cell and the protein machinery and starts duplicating the genetic material and the production of the protein capsid. Then, the newly produced genetic materials are packed inside the protein capsid. Then the lysis of the cell occurs, releasing all of the viruses, which in turn will infect other cells.
History
The use of phages started in the late 1800s. A bacteriologist from the UK discovered the presence of antibacterial substances in the waters of Ganga and Jamuna, which is responsible for limiting the spread of the cholera epidemic in these areas. The antimicrobial substance passes through fine filters and is resistant to heat. The isolation or structural characterization of these antimicrobial agents were not possible at that juncture. After two decades, Frederick Twort, a bacteriologist , suspected that these antibacterial agents are viruses. Later, Felix d’Herelle, a microbiologist at the Pasteur Institute in Paris, identified it as a bacteriophage.
The use of phages in therapy dates back to 1919, when Felix d’Herelle used bacteriophage to treat dysentery in a 12-year-old boy. He was cured by the first dose of bacteriophage, but the results of this study were not published. The first reported use of bacteriophage in therapy was in 1921 for staphylococcal skin disease. Later, due to the discovery and wide-spread use of antibiotics, phages in therapy were discontinued. Now, with the increase in antibiotic-resistance strains of bacteria called superbugs, the need for an alternative therapy has arisen which has led to the reintroduction of phages in therapy.
How does phage therapy work?
People who are severely ill or has infection with multidrug-resistant bacteria strains are treated using bacteriophages in phage therapy. Phages are host-specific; a particular phage can infect only one bacterium, which is its host. The tail of the phages attaches to a specific protein present on the surface of the target host. This attachment of the phages to the host cell is specific to each phage and bacterium. Phages are host-specific. This facilitates the attachment of the phages to the host cell. The phage genome is then inserted into the host cell. Phages are classified based on mode of replication as lytic or virulent phages and lysogenic phages or temperate phages.
Image source: Wikimedia
In phage therapy, utilises virulent phages, Since they cause lysis of the cell immediately after the completion of replication and assembly. In lysogenic phages, the phage genome is integrated into the host genome and remains in this state for a very long time. Which is not suitable for treatment purposes. In phage therapy, the virulent phages are administered intravenously, locally or subcutaneously, depending on the location and type of infection.
Benefits of Phage Therapy
Phages are bactericidal
The lytic phages used in phage therapy cause the death of the bacterial cell. They cause the lysis of the cell. In the case of some of the antibiotics, that have a bacteriostatic effect, the growth of the bacteria is inhibitted. The bacterium survives, and there is always a chance of reinfection.
A targeted approach to fighting infection
As phages are specific against a particular bacterium, they are target-specific and do not cause harm to any other cells or tissues. In this way , the infection is targeted and the pathogen, especially the bacterium, is destroyed, and the infection is eliminated without collateral damage.
Potential to combat antibiotic-resistant bacteria
Phage therapy comes to our aid when the antibiotics are not effective in fighting against the infection. In recent years, due to the excessive use of antibiotics, microorganisms have developed resistance to these antibiotics. Resistance means these antibiotics have no effect on the organism. The microorganisms have devised their own method to evade the antibiotic effects. Thus, antibiotic treatment is ineffective against these organisms. This antibiotic resistance is particularly prevalent in bacteria. In these cases, phages specific to the particular bacterium are introduced to kill these bacteria and cure the infection.
Reduced risk of side effects compared to antibiotics
The risk of using phage compared to antibiotics is very minimal. Antibiotics have many side effects. They vary depending on the antibiotic used. It can sometimes impair the proper functioning of the individual. Also, antibiotics remain in the human body many days after treatment, and traces of the antibiotics are present in milk and in feces. Thus, new mothers who are breastfeeding must restrict their use of certain antibiotics. Also, excessive and unauthorized use of antibiotics can lead to the development of multidrug resistance.
This is not the case with phages; they have only a protein coat and a nucleic acid that does not cause any reactions in humans. Also, as they are specific to the bacterium, they do not have any negative effects on humans.
Risk related to phage therapy
Benefits and risk are both two sides of the same coin; for any treatment or procedure, there will be some amount of risk. Phage therapy poses risks such as the lack of published results and the potential for septic shock. Septic shock can occur when lysed bacterial cells release their contents inside our bodies. The cellular content of bacteria can contain endotoxins, which can cause septic shock. Another risk is the change that might happen in the bacterial genome during its interaction with the phage genome, which can lead to the development of new strains of bacteria that can be difficult to eradicate.
Applications of phage therapy
Some of the areas in which phage therapy is used are
- Treating bacterial infections
- Potential use in food safety
- Phage therapy in wound care
- In the treatment of infections caused by antibiotic-resistant strains of bacteria
- In treating biofilm infections
- In the treatment of skin infections
Research and development:
The Food and Drug Administration (FDA) has approved clinical trials in phage therapy. Studies are underway for the use of phage therapy in recurrent urinary tract infections and in cystic fibrosis. Phage therapy against Escherichia coli and Salmonella enterica is in progress. In some cases, researchers have reported success in clinical treatments, but due to the limited number of randomized clinical trials, researchers cannot draw any conclusions.
Reference
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10146840/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10124553/
- Image source: wikki Commons
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC90351/
- https://asm.org/articles/2022/august/phage-therapy-past,-present-and-future
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278648/
- https://www.nature.com/articles/s41599-020-0478-4
- https://www.webmd.com/a-to-z-guides/what-is-phage-therapy
- https://www.whatisbiotechnology.org/index.php/science/summary/phage-therapy/phage-therapy-uses-viruses-that-attack-bacteria-to-trea
Written by Krishnambal.S