Bacteriophage Therapy : A Potential Therapeutic Agents
Bacteriophages are “bacteria eaters” in that they are viruses that infect and destroy bacteria. Sometimes called phages, these microscopic organisms are ubiquitous in nature. In addition to infecting bacteria, bacteriophages also infect other microscopic prokaryotes known as archaea. This infection is specific to a specific species of bacteria or archaea. A phage that infects E. coli for instance, will not infect anthrax bacteria. Since bacteriophages do not infect human cells, they have been used in medical therapies to treat bacterial diseases.
Bacteriophages have three main structure types.
Since bacteriophages are viruses, they consist of a nucleic acid (DNA or RNA) enclosed within a protein shell or capsid. A bacteriophage may also have a protein tail attached to the capsid with tail fibers extending from the tail. The tail fibers help the phage attach to its host and the tail helps to inject the viral genes into the host. A bacteriophage may exist as:
- viral genes in a capsid head with no tail
- viral genes in a capsid head with a tail
- a filamentous or rod-shaped capsid with circular single-stranded DNA.
Bacteriophages pack their genome
How do viruses fit their voluminous genetic material into their capsids? RNA bacteriophages, plant viruses, and animal viruses have a self-folding mechanism that enables the viral genome to fit within the capsid container. It appears that only viral RNA genome have this self-folding mechanism. DNA viruses fit their genome into the capsid with the help of special enzymes known as packing enzymes.
Bacteriophages have two life cycles
Bacteriophages are capable of reproducing by either the lysogenic or lytic life cycles. The lysogenic cycle is also known as the temperate cycle because the host is not killed. The virus injects its genes into the bacterium and the viral genes are inserted into the bacterial chromosome. In the bacteriophage lytic cycle, the virus replicates within the host. The host is killed when the newly replicated viruses break open or lyse the host cell and are released.
Bacteriophages transfer genes between bacteria
Bacteriophages help to transfer genes between bacteria by means of genetic recombination. This type of gene transfer is known as transduction. Transduction can be accomplished through either the lytic or lysogenic cycle. In the lytic cycle, for example, the phage injects its DNA into a bacterium and enzymes separate the bacterial DNA into pieces. The phage genes direct the bacterium to produce more viral genes and viral components (capsids, tail, etc.). As the new viruses begin to assemble, bacterial DNA may inadvertently become enclosed within a viral capsid. In this case, the phage possesses bacterial DNA instead of viral DNA. When this phage infects another bacterium, it injects the DNA from the previous bacterium into the host cell. The donor bacterial DNA then may become inserted into the genome of the newly infected bacterium by recombination. As a result, the genes from one bacterium are transferred to another.
Bacteriophages can make bacteria harmful to humans
Bacteriophages play a role in human disease by turning some harmless bacteria into agents of disease. Some bacteria species including E. coli, Streptococcus pyogenes (causes flesh-eating disease), Vibrio cholerae (causes cholera), and Shigella (causes dysentery) become harmful when genes that produce toxic substances are transferred to them via bacteriophages. These bacteria are then able to infect humans and cause food poisoning and other deadly diseases.
Bacteriophages are being used to target superbugs
Scientists have isolated bacteriophages that destroy the superbug Clostridium difficile (C. diff). C. diff typically affects the digestive system causing diarrhea and colitis. Treating this type of infection with bacteriophages provides a way to preserve the good gut bacteria while destroying only the C. diff germs. Bacteriophages are seen as a good alternative to antibiotics. Due to antibiotic overuse, resistant strains of bacteria are becoming more common. Bacteriophages are also being used to destroy other superbugs including drug-resistant E. coli and MRSA.
Bacteriophages play a significant role in the world’s carbon cycle
Bacteriophages are the most abundant virus in the ocean. Phages known as Pelagiphages infect and destroy SAR11 bacteria. These bacteria convert dissolved carbon molecules into carbon dioxide and influence the amount of available atmospheric carbon. Pelagiphages play an important role in the carbon cycle by destroying SAR11 bacteria, which proliferate at a high rate and are very good at adapting to avoid infection. Pelagiphages keep SAR11 bacteria numbers in check, ensuring that there is not an overabundance of global carbon dioxide production.
Phage therapy is a treatment approach that uses bacteriophages, which are viruses that infect and kill specific bacteria. It involves using these viruses to target and destroy bacterial infections, serving as an alternative to antibiotics.
Bacteriophages also known as “phages” are viruses that are capable of infecting bacteria. Phage comes from the Greek word phagein that means “to devour”, so bacteriophage literally means “bacteria eater”. Although it may seem odd that a virus can infect bacteria (single celled microbe) but in fact, bacteriophages are nearly 40 times smaller compared to bacteria. The bacteriophages get attached to their targeted bacteria via specific tail fibre receptors. The tail fibres happen to be one of the crucial structural elements of bacteriophages that makes each phage type specific to its host bacteria.
Phages are highly specific in their action, targeting only the specific bacteria they are programmed to attack, which can potentially reduce the risk of antibiotic resistance. Phage therapy has gained attention as a potential solution for antibiotic-resistant infections and is being explored as a promising avenue in medical research.
History
Bacteriophages are viruses that infect bacteria and use them as hosts for their replication. They are highly diverse and can target different types of bacteria. It was discovered by Frederick Willian Twort in 1915 (Great Britain) and Felix d’Herelle in 1917 (France)
In 1896, a British bacteriologist named Ernest H Hankin observed that the waters from Yamuna and Ganga contained some biological principle which destroyed cholera-inducing bacteria. He also observed that millipore filters that were known to retain microorganisms like bacteria, couldn’t stop this substance from passing through. In 1915, another British bacteriologist named Frederick Twort discovered a small agent capable of infecting and killing a bacteria. Two years after the discovery made by Twort, Felix d’Herelle, a French-Canadian microbiologist observed a similar finding while studying patients recovering or suffering from bacillary dysentery. It was in fact d’Herelle who started bacteriophages use in clinical medicine and brought to light the “phage therapy” concept. After the invention of the electron microscope, a German doctor named Helmut Ruska came up with the first physical description of the bacteriophages. Following his observations, Luria and Anderson visualised various types of bacteriophages and described their common structure. In the subsequent years, considerable progress was made in the field of bacteriophages with the first human experiments staring in the 2000s.
Bacteriophage Lifecycle
Similar to other viruses, bacteriophages need to infect their targeted bacteria to reproduce. The infection process involves a series of steps which can be referred to as the ‘phage lifecycle’. There are two cycles, while certain bacteriophages reproduce only via a lytic cycle, other bacteriophages alternate between a lysogenic lifecycle and lytic lifecycle. In a lytic lifecycle, the bacteriophages cause lysis of the targeted bacterial cells by bursting the cell wall of bacteria. In a lysogenic lifecycle, the bacteriophages doesn’t kill the targeted bacteria cell, instead they are replicated along with the bacterial cell DNA every time the cell divides.
Lytic Cycle
The characteristics of a bacteriophage in a lytic cycle is typical to that of a virus; after attachment to their targeted bacterial cell the resources of the cell is utilised to produce new phages. This causes the cell to burst and lysis of the bacteria. The phases of the lytic cycle: • Binding: The bacteriophage tail attaches to a specific receptor present on the bacterial cell’s surface. • Invasion: The phage genome enters the cytoplasm of the bacteria. • Biosynthesis: The phage DNA replicates and translates the important viral components to make phage proteins. • Maturation: New phage particles are created. • Lysis: The cell expands and bursts releasing the newly created phages.
Lysogenic Cycle
In the lysogenic cycle, the initial two phases are identical to that of the lytic cycle. However, after the phage DNA enters the cell, it recombines with the bacterial chromosome causing the phage genome DNA to integrate into the chromosome. The integrated phage DNA is also known as a prophage. Thus, every time the bacteria replicates its chromosome, the phage’s DNA is also replicated and passed along to new cells during reproduction. The phases of the lysogenic cycle: • Binding: The bacteriophage attaches to the host. • Invasion: It injects the DNA into the host cell. • Integration: The DNA of the phage recombines with bacterial chromosome. • Cell Division: The phage DNA is passed onto the new cells after cell division. If the conditions become stressful, the prophage DNA comes out of the bacterial chromosome to enter the lytic cycle.
Bacteriophages – Alternative to Antibiotics
Before Alexander Fleming discovered antibiotics in 1928, considerable research was conducted on bacteriophages to treat bacterial infections. Though research on phage was abandoned in various parts of the world post the discovery of antibiotics, but in different Soviet nations the developments continued mostly because of the lack of western antibiotics. Of late, owing to increasing problems of antibiotic resistance, there has been a resurgence of interest in the “phage approach”. In fact, bacteriophage therapy is being used nowadays to help fight different bacterial diseases in animal and poultry. Leading the way, Proteon Pharmaceuticals has emerged as a prominent name focused on improving animal and human health with their sustainable bacteriophage products and solutions. Using precision biology for microbiome protection, Proteon Pharmaceuticals aims to reduce the unnecessary use of antibiotics to enhance on-farm productivity and enhance environmental sustainability of livestock production.
Compiled & Shared by- Team, LITD (Livestock Institute of Training & Development)
Image-Courtesy-Google
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APPLICATION OF BACTERIOPHAGE THERAPY IN FARM ANIMALS TO REDUCE ANTIBIOTIC USE
