Phage Life Cycle: From Lysis to Lysogeny

Viruses that infect bacteria, known as bacteriophages or phages, play a crucial role in microbial ecosystems and biotechnology. Unlike cellular organisms, they rely entirely on bacterial hosts to reproduce, making their life cycle a fascinating study of molecular control and adaptation.

Phages follow different infection pathways based on environmental conditions and host factors. Understanding these pathways aids applications like bacterial control and gene therapy.

Lytic Infection Steps

The lytic cycle begins when a phage attaches to a susceptible bacterial cell. This attachment is highly specific, as phages recognize unique receptor molecules on the bacterial membrane. For instance, T4 bacteriophage, which infects Escherichia coli, binds to lipopolysaccharides and outer membrane proteins, ensuring only compatible hosts are targeted. Once anchored, the phage injects its genetic material—either DNA or RNA—into the bacterial cytoplasm while the empty capsid remains outside. This process, known as penetration, is facilitated by enzymatic degradation of the bacterial cell wall or membrane, allowing the viral genome to bypass cellular defenses.

Once inside, the viral genome hijacks the host’s transcriptional and translational machinery. Early viral genes are expressed almost immediately, encoding proteins that suppress bacterial defenses and redirect resources toward phage production. Some of these proteins degrade bacterial DNA to prevent a host response. Meanwhile, phage polymerases modify host RNA synthesis to prioritize viral gene transcription. Studies on T7 phage show that within minutes of infection, host RNA polymerase is altered to favor viral transcription, accelerating replication.

As replication progresses, structural components such as capsid proteins and tail fibers are synthesized and assembled. This process is highly coordinated, with scaffolding proteins ensuring proper folding and structural integrity. In phages like T4, DNA is packaged into pre-formed capsids through a molecular motor that exerts significant force to compact the genome. Once packaging is complete, tail structures are attached, finalizing infectious particles. This process is remarkably efficient—within a single bacterial cell, hundreds of new phages can be assembled in under an hour.

Lysogenic State And Prophage Formation

Some phages, known as temperate phages, integrate their genetic material into the host genome, establishing a lysogenic state. This regulatory decision is influenced by environmental conditions and host factors. If conditions are unfavorable for immediate replication—such as nutrient scarcity or high bacterial population density—the phage may opt for lysogeny. This decision is governed by molecular regulators, including phage-encoded repressors that inhibit lytic gene expression, shifting the viral lifecycle toward dormancy.

Once lysogeny is chosen, the phage genome, now a prophage, integrates into the bacterial chromosome through site-specific recombination. This process, mediated by phage-encoded integrases, ensures stable incorporation. In λ phage, the integrase enzyme facilitates recombination between the attP site on the phage genome and the attB site on the bacterial chromosome. The prophage is then passively replicated alongside the bacterial genome during cell division, ensuring persistence across generations without harming the host.

As long as the prophage remains integrated, it remains transcriptionally silent due to repressors such as CI in λ phage. These repressors bind to operator regions within the phage genome, preventing activation of lytic genes. This repression system is highly stable, allowing the prophage to persist for extended periods. However, lysogeny is not merely passive; prophages can influence bacterial physiology in profound ways. Some prophages carry genes that enhance bacterial survival, such as toxins that contribute to pathogenicity or resistance mechanisms that provide a competitive advantage. The diphtheria toxin produced by Corynebacterium diphtheriae, for example, is encoded by a prophage, demonstrating how lysogeny can alter bacterial virulence.

Transition Between Lytic And Lysogenic States

Environmental shifts and cellular stressors can disrupt lysogeny, prompting prophages to excise from the bacterial genome and re-enter the lytic cycle. This transition is often triggered by DNA damage, oxidative stress, or antibiotic exposure, which activate bacterial SOS repair pathways. In Escherichia coli, the SOS response induces RecA, a protein that facilitates the autocleavage of phage repressors such as CI in λ phage. As repression weakens, lytic genes are reactivated, initiating prophage excision and virion production.

Once excised, the prophage undergoes circularization or repair before replication resumes. Some phages employ excisionases and recombinases to facilitate precise removal from the bacterial chromosome, minimizing disruption. In cases of incomplete or imprecise excision, portions of bacterial DNA may be inadvertently packaged into new phage particles, leading to horizontal gene transfer through specialized transduction. This mechanism has been implicated in the spread of antibiotic resistance genes and virulence factors among bacterial populations, highlighting the broader ecological implications of lysogeny-to-lysis transitions.