Bacteriophage

DISCOVERY AND INTRODUCTION

· Bacteriophages were discovered independently Twort 1915 in the U.K and Hérelle 1917 in France and the term was coined by Hérelle.

Bacteriophage or Phage is a virus that infects and replicates only within the body of bacteria and no other organism.

· Highly species-specific towards their host cell. The bacteriophages only infect a single species of bacteria or even specific strains of bacteria within a species.

· Have potential to destroy bacterial suspension and called Twort d Herelle Phenomenon.

· Bacteriophages attacking Escherichia coli are called coliphages or T-phages.

· Like all viruses, phages are simple entities that consist of a core of genetic material (nucleic acid) surrounded by a protein capsid.

· The nucleic acid may be either DNA or RNA and may be double-stranded or single-stranded.

· The International Committee on Taxonomy of Viruses had classified the phages based on the nature of their nucleic acid, morphology and physicochemical properties of their virion particles. Currently, ICTV has classified the bacteriophages into nine orders, 48 families with 32 subfamilies, and 317 genera.

· By morphology phages can be tailed phages, polyhedral or filamentous phages.

STRUCTURE (T-EVEN PHAGE)

· The virion of T-even phage is tadpole like structure with a hexagonal head connected to a helical tail through a short collar.

· The head is about 95 nm in length and 65 nm in diameter and composed of about 2000 capsomeres arid encloses a tightly packed nucleic acid.

· The linear dsDNA (50 nm long) is coiled, very long and it is genetic material of phage particles and induces the host cell to synthesize more and more phage particle.

· The tail has an inner hollow tube called core, surrounded by a contractile sheath which consists of 24 annular rings. The distal end of the tube is connected to a hexagonal basal plate with spike or tail spin at each corner. Six long, flexible tailfibers (150 nm) arise from the basal plate which helps the bacteriophage to attaches to the bacteria.

LIFE CYCLE

Depending upon the interaction of phages with the bacterial cells they have been distinguished into two major types of life cycle.

• Lytic Cycle or Virulent Cycle or Infective Cycle (Virulent Phage): Type of lifecycle where the viral DNA remains as a free-floating molecule and replicates separately from the bacterial DNA.

• Lysogenic Cycle or Temperate Cycle (Non or Avirulent Phage): is defined by the incorporation of the bacteriophage genome into the host genome

Lytic Cycle

In the Lytic Cycle, a bacteriophage infects a bacteria and kills it to release progeny virus. There are five stages in the bacteriophage lytic cycle.

1) Attachment. The bacteriophage attaches itself on the surface of bacteria (adsorption). The tips of the tail fibres attach to specific receptorse.g., lipopolysaccharides, OmpC protein on host surfaces (bacterial cell).

2) Penetration. Lysozyme digest the host cell wall and the tail sheath contracts, which acts like a hypodermic needle to inject the viral genome (DNA) in the host cell. The phage head and remaining components remain outside the bacteria called Ghosts or Doughnut.

3) Biosynthesis of new viral components. After entering the host cell, the virus synthesizes virus-encoded endonucleases to degrade the bacterial chromosome. It then hijacks the host cell to replicate, transcribe and translate the necessary viral components (capsomeres, sheath, base plates, tail fibers, and viral enzymes) for the assembly of new viruses

4) Maturation and Assembly: On maturation, the head and tail protein of phage DNA assemble and each component of phage DNA is surrounded by a protein coat. Ultimately, the tail structures are added forming a virion.

5) Release: The infected bacterial cell is lysed releasing the progeny phages and the progeny viruses are liberated into the environment to infect new cells. The phage enzymes weaken the cell wall of bacteria during replication.

Lysogenic Cycle

· In a lysogenic cycle, the phage genome enters the cell through attachment and penetration. A prime example is the lambda phage.

· During the lysogenic cycle, instead of killing the host, the phage DNA integrates into the bacterial chromosome and becomes part of the host. The integrated phage genome (DNA) is called a prophage.

· A bacteria carrying a prophage without being lysed is called a lysogen and the process is called lysogeny.

· As the bacteria replicate its chromosome, it also replicates the phage’s DNA and passes it on to new daughter cells during reproduction.

· The presence of the phage may alter the phenotype of the bacterium, since it can bring in extra genes. This change in the host phenotype is called lysogenic conversion or phage conversion. In the case of V. cholera, phage encoded toxin can cause severe diarrhea and in C. botulinum, the toxin can cause paralysis and both are are less virulent in the absence of the prophage.

· During lysogeny, when the host cell face harsh condition then the prophage shows induction, which results in the excision of the viral genome from the host chromosome. After induction the temperate phage follows the lytic cycle and then again undergoes lysogeny in a newly infected cell.

· The lytic cycle doesn’t allow genetic recombination of the host chromosome whereas the lysogenic cycle allows the genetic recombination of the host chromosome.

Economic importance

Advantages of Bacteriophage

· Phages are very specific and do not harm the useful bacteria that live in and on the body.

· They have been proposed as alternatives to antibiotics for many antibiotic resistant bacterial strains.

· Have been used in treatment against dysentery, chlorea, plague and many other pathogenic bacterial diseases.

· Useful in the lysis of bacterial present in polluted water.

· Helps in transduction of genetic material and therefore they have potential uses in biotechnology, research, and therapeutics.

· Phages can be used as bio control agents in agriculture and petroleum industry.

· Phages can be administered orally, incorporated in drinking water or food to control Salmonella and Campylobacter in poultry

· Phages are also excellent as food bio preservation agents.

Disadvantages of Bacteriophages

· In comparison to chemical molecules, phages are relatively large. For this reason, the sites in the body that can be reached by them must be carefully clarified.

· Phages that are injected into the bloodstream are recognized by the human immune system. Some of them are quickly excreted and, after a certain period, antibodies against the phages are produced by the body. For this reason, it appears that one type of phage can only be used once for intravenous treatment.