What is Bacteriophage?
Bacteriophages, also known as phages, are viruses that infect and replicate only in bacterial cells. They are ubiquitous in the environment and recognized as the earth’s most abundant biological agent.
They are extremely diverse in size, morphology, and genomic organization. However, all consist of a nucleic acid genome encased in a shell of phage-encoded capsid proteins, which protect the genetic material and mediate its delivery into the next host cell.
Electron microscopy has allowed the detailed visualization of hundreds of phage types, some of which appear to have “heads,” “legs,” and “tails.” Despite this appearance, phages are non-motile and depend upon Brownian motion to reach their targets.
Brief History Of Bacteriophage Discovery And Research
Phages were independently discovered by Frederick Twort in England and Felix d’Herelle, in Paris at the Pasteur Institute.
Twort was trying to produce a vaccine against a virus without a host cell in an artificial medium while D’Herelle was studying an extreme outbreak of dysentery among the soldiers in Paris during the First World War, when he discovered bacteriophage, a bacterium feeding body.
He applied this to bacterial culture and observed that turbid cultures turned into clear indicating the lytic nature of bacteriophages against bacteria.
His thesis on the bacteriophage was published in a monograph, “The bacteriophage and its behavior”, along with several other books and papers subsequently.
This research laid the foundation of “bacteriophagology”. A new vocabulary was used to describe post-infection activities and explained the purification and titration of bacteriophage culture in some detail.
Structure of Bacteriophages
Like other viruses, bacteriophages vary in size and morphology. However, under an electron microscope, they comprise a nucleic acid molecule surrounded by a protein structure. There is a tail attached to its head through a neck.
A T4 bacteriophage consists of the following parts:
1. Head (Capsid)
The head of bacteriophages, more commonly known as the capsid, forms the protective casing that encloses the genetic material of the phage. This genetic material is either DNA or RNA, depending on the type of bacteriophage.
Capids are made of protein subunits known as capsomeres arranged in polyhedral or helical forms. The structural integrity of the capsid is vital for protecting the enclosed genetic material from external factors, ensuring its safe delivery into the bacterial host.
2. Tail
The tail extends from the head, resembling the lander of a lunar spacecraft. It is not only a physical appendage but facilitates the initial attachment to the surface of a bacterial cell, initiating the infection process.
It consists of the following parts:
Collar
The collar is a specialized region at the base of the tail, connecting it to the head. It acts as a transition zone, facilitating the transfer of genetic material from the head to the bottom during infection. The collar thus ensures the seamless coordination of the various components of the phage.
Sheath
The sheath is a tubular structure extending from the collar, surrounding and protecting the tail tube. It is critical in injecting the phage’s genetic material into the bacterial host.
As the sheath attaches to the bacterial cell, it contracts, propelling the tail tube and genetic material into the host cell. It is a mechanism similar to an injection syringe that injects fluids into our body.
Baseplate
At the lower end of the tail, the baseplate serves as the anchoring point for the tail fibers, with a spike in the center. It is a complex structure with receptor-binding proteins that interact specifically with surface receptors on the bacterial cell.
Characteristics of bacteriophages
Life Cycle of Bacteriophages
There are two ways by which bacteriophages infect the host bacterium.
Lytic Cycle (Virulent infection)
They induce complete lysis of the bacterial cell, which is known as a lytic life cycle. Examples include T2, T4, T6 (T-even phages), they are also known as virulent phages. The bacterial cell is completely destroyed immediately after replication of the viral genome. This type of infection is called virulent infection and it is mostly used for phage therapy.
The lytic cycle has the following steps:
- Adsorption- Anchoring of bacteriophage to the bacterial cell wall with the help of tails fibres.
- Penetration– The phage DNA gets injected into bacteria.
- Replication and synthesis– The bacterial DNA is disrupted and the viral genome takes charge of bacterial machinery. It starts making proteins required for replication and other structural proteins.
- Assembly– Phage components are assembled into new viral particles.
- Lysis and release– Bacterial cells are lysed and new viral particles are liberated to infect other cells.
Lysogenic Cycle (Temperate infection)
Bacteriophages that undergo lysogeny are known as temperate phages. The viral DNA gets integrated into the host genome and replicates along with the bacterial genome. The integrated viral genome is known as a prophage.
It is relatively harmless and continues to remain in the position until the lytic cycle is triggered. It may be spontaneous or due to certain external conditions such as radiation exposure. Then the prophage becomes active and a lytic cycle initiates resulting in the lysis of the cell wall.
After penetration, the phage DNA gets integrated into bacterial DNA and gets replicated along with the bacterial genome.
As the bacterial genome is inserted into the bacterial genome and bacteria continue to perform the normal activities, the viral genome gets transferred to the progenies as well.
Bacterial cells containing a prophage are called lysogenic cells. The lysogenic cells (having a prophage) may exhibit new properties, e.g. Corynebacterium diphtheriae and Clostridium botulinum, when containing certain prophage DNAs, synthesize toxins, which are harmful.
Examples of lysogenic phage include lambda (λ) phage. Due to the ability to insert their genome specifically and replicate, they are used in genetic recombination.
To lyse or not to lyse?
How does a phage “decide” whether to enter the lytic or lysogenic cycle when it infects a bacterium? One important factor is the number of phages infecting the cell at once. Larger numbers of co-infecting phages make it more likely that the infection will use the lysogenic cycle.
This strategy may help prevent the phages from wiping out their bacterial hosts (by toning down the attack if the phage-to-host ratio gets too high).
When there are multiple phages infecting a single bacterium, that suggests (statistically speaking) that the phages may be in danger of wiping out their bacterial hosts.
Phages that flip to the lysogenic mode in response to a high multiplicity of infection may be less likely to run out of hosts and “die out” as a population (because they can strategically stop killing hosts once their own numbers get too high).
Notably, once a cell has a prophage in its genome, it is immune to being infected by another phage of the same type.
Thus, the genetically encoded tendency to flip to lysogeny at at high multiplicity might have been favored by natural selection (explaining why phages have it today).
What triggers a prophage to pop back out of the chromosome and enter the lytic cycle? At least in the laboratory, DNA-damaging agents (like UV radiation and chemicals) will trigger most prophages in a population to re-activate. However, a small fraction of the prophages in a population spontaneously “go lytic” even without these external cues.
Significance of Bacteriophages
Although bacteriophages cannot infect and replicate in human cells, they are an important part of the human microbiome and a critical mediator of genetic exchange between pathogenic and nonpathogenic bacteria.
The transfer of genes from 1 bacterial strain to another by a bacteriophage is called transduction and can occur in a generalized or specific manner.
Bacteriophages have widespread applications in the study of biotechnology and medicine.
In Genetic Engineering
Due to their relatively simple structures and lifecycles, bacteriophages are ideal model organisms for studying fundamental genetic processes.
Their ability to infect bacteria allows scientists to introduce specific genes into bacterial cells, facilitating the production of desired proteins or modifying genetic material.
Alternative to Antibiotics
With rising antibiotic resistance, bacteriophages are garnering attention as potential alternatives to traditional antibiotics. Phage therapy involves using specific bacteriophages to target and eliminate bacterial infections, offering a tailored and potentially more effective approach.
Controlling Bacterial Population
Bacteriophages are also used to maintain the health of an ecosystem. It does so by controlling the bacterial population in the ecosystem under study.
In agriculture, bacteriophages have shown promise in controlling the unwanted bacterial population to increase the yield of crops.