Life Cycle of Bacteriophages

Life Cycle of Bacteriophages: Bacteriophages exhibit two different types of life cycles: 

  1. Lytic or virulent cycle: In the virulent cycle, there is intracellular multiplication of phages followed by lysis and release of progeny virions. This is called the lytic cycle. 
  2. Temperate or avirulent or lysogenic cycle: In the lysogenic cycle the phage DNA  becomes integrated with the bacterial genome, replicating synchronously without any cell lysis. 

Lytic cycle of bacteriophages

The replication of virulent phages was initially studied using the T-even numbered  (T2, T4, and T6) phages of E. coli. The multiplication cycle of these phages like that of all viruses occurs in five stages (Fig.1). 

  1. Attachment or adsorption 
  2. Penetration 
  3. Biosynthesis of phage components 
  4. Maturation 
  5. Release of progeny phage particles. 

1. Attachment or adsorption: The first step in the infection of a host bacterial cell by a  phage is adsorption. Phage particles come into contact with bacterial cells by random collision. A phage attaches to the surface of a susceptible bacterium by its tail. Adsorption depends on the presence of complementary chemical groups on the receptor sites of the bacterial surface and the terminal base plate of the phage. In some cases, the specific receptor of the bacterium is part of the bacterial lipopolysaccharide, although any surface structure can function as a specific phage receptor, including flagella, pili, carbohydrates, and proteins in the membrane or cell wall. Host specificity of phages is determined at the level of adsorption. Experimental infection by direct injection of phage DNA can be achieved even in bacterial strains that are insusceptible to infection by the whole phage. The infection of a  bacterium by the naked phage nucleic acid is known as ‘transfection’.

Lytic growth cycle of bacteriophage 
Fig.1: Lytic growth cycle of bacteriophage

2. Penetration: Attachment is followed by injection of DNA (nucleic acid) into the bacterial cell. The phage DNA is injected into the bacterial body through the hollow core.  Penetration may be facilitated by the presence of the phage tail of lysozyme which breaks a  portion of the bacterial cell wall for the entry of the phage DNA. The phage DNA alone is necessary for the initiation of the synthesis of daughter phages. After penetration of DNA,  the empty head and tail of the phage remain outside the bacteria called ‘shell or ghost’. The processes of adsorption and penetration are shown in Fig.1. If many phages are attached to the bacterial cell, multiple holes are produced on the cell with the consequent leakage of the cell contents. Bacterial lysis occurs without viral multiplication. This is known as ‘lysis from without’. Phages such as T1 and T5, that do not have a contractile sheath also inject their nucleic acid through the cell envelope by adhesion sites between the inner and outer membranes. 

3. Biosynthesis of phage components: After infection and penetration of DNA,  transcription of a part of the viral genome produces ‘early’ mRNA molecules, which are translated into a set of ‘early’ proteins. These serve to switch off host cell macromolecular synthesis, degrade the host DNA and start to make components for viral DNA. The viral DNA  replicates and also starts to produce a batch of ‘late’ mRNA molecules, transcribed from genes that specify the proteins of the phage coat. These late messages are translated into the subunits of the capsid structures, which condense to form phage heads, tails, and tail fibers. 

4. Maturation: Phage DNA, head, and tail protein are synthesized separately in the bacterial cell. The DNA is condensed into a compact polyhedron and ‘packaged’ into the head and finally, the tail structures are added. The process of assembly of the phage from its components is called ‘maturation’. 

5. Release of progeny phage particles: The release of progeny phage particles takes place by explosion or bursting (lysis) of the bacterial cell wall. Lysozyme synthesized within the cell causes the bacterial cell wall to break down and the newly produced bacteriophages are released from the host cell. The released bacteriophages infect other susceptible bacterial cells. Each cycle of phage reproduction may require 20 to 60 mins and a single phage infection may produce 200 or more progeny. 

The sequence of events by the injection of the phage nucleic acid and release of newly synthesized virions is called the ‘replication cycle or viral multiplication’. The interval between the entry of the phage DNA into the bacterial cell and the appearance of the first infectious intracellular phage particle is known as the ‘eclipse phase’. It represents the time required for the synthesis of the phage components and their assembly into mature phage particles. The interval between the infection of a bacterial cell and the first release of infectious phage particles is known as the ‘latent period’. Immediately after the latent period, the number of phage particles released increases for a few minutes till the maximum number of daughter phages is reached. This period, during which the number of infectious phages released rises is known as the rise period. 

Temperate or avirulent or lysogenic cycle: 

In contrast to virulent phages, temperate phages don’t cause lysis of the host cell.  Following the entry into the host cell, the temperate phage nucleic acid becomes integrated with the bacterial chromosome. The integrated phage nucleic acid is known as the  ‘prophage’. The prophage behaves like a segment of the host chromosome and replicates synchronously in the bacterial cell. This is called ‘lysogeny’ and a bacterium that carries a  prophage within its genome is called a ‘lysogenic bacterium’ (Fig.2). The prophage confers certain new properties on the lysogenic bacterium. This is known as ‘lysogenic conversion’ or ‘phage conversion’. A lysogenic bacterium is resistant to reinfection by the same or related phages. This is known as ‘superinfection immunity’. 

Every time the host cell’s machinery replicates the bacterial chromosome, it also replicates the prophage DNA. The prophage remains latent within the progeny cells. However, a rare spontaneous event or the action of UV light or certain chemicals can lead to the excision of the phage DNA and initiation of the lytic cycle. This is known as ‘spontaneous induction of prophage’.

Lysogenic life cycle of a bacteriophage
Fig.2: Lysogenic life cycle of a bacteriophage
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