Two Pathways: Lysis or Coexistence
Unlike virulent strains, temperate bacteriophages have two possible life cycle pathways after entering a host cell.
The first pathway is the productive (lytic) cycle. It follows the classic sequence: the virus enters the cell, its genome replicates, new virions are assembled, and the process ends with the death (lysis) of the host bacterium.
The second pathway is the integrative (lysogenic) cycle. In this case, the host cell is not destroyed. The viral DNA enters the cytoplasm, circularizes, and integrates into the bacterial chromosome via recombination. The integrated viral DNA is called a prophage, and the bacterium carrying this genome is termed a lysogenic strain. With each cell division, the prophage is replicated synchronously and passed on to daughter cells. This state of peaceful coexistence is known as lysogeny.
Importantly, integration does not occur randomly, but at specific homologous sites. For example, in Escherichia coli, integration of lambda phage occurs at a strictly defined locus located between the galactose and biotin metabolic genes.
Maintenance of Lysogeny and Immunity
The essence of lysogeny is that the production of new phage progeny is completely blocked, preventing cell destruction. This status quo is genetically controlled. The prophage genes encode the synthesis of a specific low-molecular-weight protein called the repressor protein. This protein acts as the primary regulatory switch. Its mechanism of action is simple: the repressor inhibits transcription of the viral genome regions responsible for vegetative replication.
The presence of the repressor in the cytoplasm results in an interesting phenomenon: immunity of lysogenic bacteria. If DNA from a similar (homologous) phage attempts to enter the cell, superinfection occurs. However, the new virus cannot replicate because the repressor protein immediately blocks the incoming viral DNA from entering the vegetative state, preventing cell lysis.
Prophage Induction: Return to Lysis
The term "lysogeny" implies only the potential capability of the cell to undergo lysis. The transition from the latent state to the active state is reversible and is called induction (or derepression). During induction, the prophage excises from the bacterial chromosome, viral components are synthesized, new virions are assembled, and the cell dies. The basis of this mechanism is the inactivation of the repressor protein by external factors.
There are two types of induction:
- Spontaneous: Occurs naturally at a very low frequency ($10^{-2}$ to $10^{-6}$). Due to this rarity, mass culture lysis is not observed.
- Induced: Triggered artificially by exposure to mutagens. Physical agents include ultraviolet and ionizing radiation. Chemical agents include peroxides, mitomycin C, and others.
In biotechnology, spontaneous induction poses serious risks: sudden lysis of industrial producer bacteria can lead to the loss of a valuable product, such as a batch of antibiotics or vitamins. Conversely, in genetic engineering, induced induction is actively applied for research purposes.
Phage Conversion and Plasmid Localization
The integrated viral genome can confer new biological properties on the host—morphological, biochemical, cultural, or antigenic. This phenomenon is called phage conversion.
The classic clinical example involves the causative agent of diphtheria (Corynebacterium diphtheriae). This bacterium produces its primary pathogenicity factor, diphtheria exotoxin, exclusively when harboring a specific prophage. Without phage integration, the bacterium remains nontoxigenic.
Exceptions to the general behavior of temperate phages include:
- Defective phages. These have permanently lost the ability to form complete viral particles and cannot complete their developmental cycle either naturally or via artificial induction.
- Plasmid localization. The genome of certain phages (e.g., phage P1) does not integrate into the bacterial chromosome. Instead, it exists autonomously in the cytoplasm like a plasmid. Such autonomous viruses are widely used as vectors in genetic engineering for targeted gene transfer.