Lifecycle and structure of bacteriophage

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Bacteriophage: Structure and Lifecycle

1. Overview

Bacteriophages (phages) - literally "eaters of bacteria" - are viruses that infect bacteria. They are small structures, 50 to 200 nm in size, and are found in enormous abundance across the biosphere (estimated ~10^31 distinct phages globally). Their host range can be narrow, but every bacterium is vulnerable to some phage. Phages cannot reproduce independently; they must replicate within a bacterial host.

Goodman & Gilman's The Pharmacological Basis of Therapeutics, p. 1194

Medical Microbiology 9e, p. 535

2. Structure

The classic tailed bacteriophage (e.g., T4 phage, lambda phage) has several distinct structural components:

Component	Description
Head (Capsid)	Icosahedral protein shell that encapsidates the phage genome (usually dsDNA)
Genome	Usually double-stranded DNA; some phages carry ssRNA or ssDNA
Tail	Hollow tube used to inject the genome into the host cell; acts like a syringe
Tail fibers	Long protein filaments at the base of the tail; mediate specific binding to bacterial surface receptors
Baseplate	The distal end of the tail; connects tail fibers and initiates contraction for DNA injection

Key structural point: only the nucleic acid genome enters the host cell - the protein capsid is shed at the bacterial surface. Some phage virion proteins that are tightly associated with the nucleic acid may accompany the genome into the cell.

Sherris & Ryan's Medical Microbiology, 8th Ed., p. 208

Goodman & Gilman's, p. 1194

3. The Two Lifestyles: Lytic vs. Lysogenic

Bacteriophages have two fundamental lifecycles:

Bacteriophage life cycles - lytic and lysogenic

Figure: Bacteriophage life cycles. A: Lytic cycle. B: Temperate (lysogenic) cycle. - Goodman & Gilman's

A. Lytic Cycle (Virulent Phage)

The lytic cycle has a single outcome: host cell destruction. It proceeds through these stages:

Adsorption (Attachment) - Tail fibers bind to specific receptors on the bacterial cell wall. This interaction is highly specific and determines host range.
Penetration (Injection) - The tail contracts and injects the phage DNA through the hollow tail structure into the bacterial cytoplasm. The capsid remains outside. This is the "syringe" mechanism.
Eclipse Phase - Infectious phage particles transiently disappear. The phage genome takes over the host's replicative machinery. Host genome is inactivated ("hijacked"). Phage genes are transcribed and translated.
Biosynthesis - New phage genomes are replicated, and structural proteins (capsid, tail components) are synthesized separately.
Assembly (Maturation) - New phage genomes are packaged into new capsids and assembled into complete virions.
Lysis and Release - Phage enzymes lyse the bacterial cell wall, releasing a burst of ~100 new phage progeny that can infect further bacteria.

Goodman & Gilman's, p. 1194-1195

Sherris & Ryan's, p. 207-208

B. Lysogenic Cycle (Temperate Phage)

Temperate phages (e.g., lambda, phage β carrying diphtheria toxin gene) can choose an alternative fate:

Attachment + DNA Injection - Same initial steps as the lytic cycle.
Circularization - The injected linear phage DNA circularizes within the host cell.
Integration (Lysogeny) - Instead of immediate replication, the phage DNA integrates into the host chromosome as a prophage. The bacterium is now called a lysogen.
Stable Replication - The prophage is replicated passively as part of the bacterial chromosome each time the bacterium divides - passed to all daughter cells silently.
Induction (Excision) - When the lysogen encounters DNA-damaging stimuli (e.g., UV radiation, chemical mutagens), the SOS response is triggered. The dormant prophage becomes induced, excises from the host chromosome, and enters the lytic cycle.

Alternate lytic and lysogenic lifestyles of bacteriophage lambda

Figure: Lytic and lysogenic pathways of phage lambda. Steps 1-3: attachment, DNA injection, circularization. Steps 4-5: lysogenic integration. Steps 6-8: lytic replication and host lysis. Steps 9-10: induction from prophage state. - Harper's Biochemistry, 32nd Ed.

4. The Lambda (λ) Genetic Switch

The decision between lytic and lysogenic pathways is a beautifully regulated molecular switch, centered on an 80-bp region called the "right operator" (O_R):

Lysogenic state: The cI repressor gene is active. It represses lytic genes (including the cro gene), keeping the phage dormant.
Lytic state: The cro gene is active. It represses the cI repressor, committing the phage to lysis.
Poor growth conditions (nutrient stress) favor lysogeny; good growth conditions favor the lytic pathway.
This switch is analogous to regulatory switches seen in eukaryotic viruses like HIV and herpes simplex virus.

Harper's Illustrated Biochemistry, 32nd Ed., p. 437

5. Medical Significance of Lysogeny

Lysogeny is not merely an academic curiosity - it has direct clinical importance:

Toxin genes carried by prophages: Lysogenic bacteriophages can encode toxins. For example:
- Corynephage beta carries the gene for diphtheria toxin - a bacterium is only toxigenic if infected by this phage
- Other phage-encoded toxins include cholera toxin (V. cholerae) and certain Shiga toxins
Horizontal gene transfer (Transduction): Phages can accidentally package bacterial DNA and transfer it between bacteria, spreading antibiotic resistance genes and virulence factors

Medical Microbiology 9e, p. 538

6. Phage Therapy (Clinical Relevance)

With growing antibiotic resistance, interest in phage therapy has re-emerged. Phages act as "living antibiotics" with self-amplifying, self-limiting action at sites of infection. Phage therapy continued through the 20th century in Russia and Eastern Europe while falling out of favor in the West, but is now being reconsidered as the antimicrobial pipeline struggles with multidrug-resistant organisms.

Goodman & Gilman's, p. 1194

Summary Table

Feature	Lytic Phage	Temperate Phage
Outcome of infection	Always lyses the host	Can lyse OR integrate
Prophage formation	No	Yes
Host cell survival	No	Yes (until induction)
Induction trigger	N/A	UV, DNA damage (SOS)
Clinical example	T4 phage	Lambda phage, corynephage beta
Toxin carriage	Rare	Yes (diphtheria, cholera)

Bacteriophage handmade diagram

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A handmade hand-drawn sketch style diagram of a bacteriophage structure, drawn with pencil or pen on white paper look. Label all parts clearly with handwritten-style annotations and arrows: Head (icosahedral capsid containing DNA), Collar, Tail sheath, Tail tube (core), Baseplate, Tail fibers, and DNA inside the head. Show the classic T4 bacteriophage shape with a hexagonal head and long contractile tail. Include a small inset showing the phage injecting DNA into a bacterial cell wall. Use a clean, educational biology textbook sketch aesthetic with neat hand-lettered labels.

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Handmade diagram of bacteriophage

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A handmade pencil sketch diagram of a bacteriophage (T4 phage) on white paper, drawn in a biology student notebook style. The diagram shows the classic bacteriophage shape with a large hexagonal head containing coiled DNA strands inside, a collar below the head, a long contractile tail sheath with crosshatched lines, a central tail tube, a hexagonal baseplate at the bottom, and six long spidery tail fibers extending outward from the baseplate. All parts are labeled with neat handwritten arrows pointing to: Head, DNA, Collar, Tail sheath, Tail tube, Baseplate, Tail fibers. The sketch uses pencil shading, looks like a hand-drawn biology diagram, slightly imperfect lines giving it an authentic hand-drawn feel.

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