History of discovery and visualization
The term originates from the Greek word phagos — devouring. The spontaneous destruction (lysis) of anthrax causative agent bacteria was first observed by the Russian scientist N.F. Gamaleya in 1898. Later, in 1915, the Englishman F. Twort described the ability of a filtrate to dissolve staphylococcal culture.
A key contribution was made by the Frenchman F. d'Hérelle (1917): he isolated a lytic agent from the feces of dysentery patients, proved its viral nature, and proposed the term «bacteriophage».
Macroscopically, the action of phages looks very characteristic:
- In liquid medium: a turbid bacterial culture completely clarifies.
- On solid medium: when phage is applied to a confluent bacterial «lawn», round sterile spots form — they are called negative colonies or «plaques».
Morphology and structure of complex phages
According to their shape, phages are divided into small cubic, filamentous, and spermatozooid forms. The large spermatozooid-shaped phages (e.g., T-series coliphages) have been studied the most. Their structure includes three main parts:
- Head. Has an icosahedral (cubic) type of symmetry, with a size of 65–100 nm. It consists of a protein capsid, inside of which a nucleic acid molecule (most commonly double-stranded circular DNA) is tightly packed. A histone-like protein is located there for DNA supercoiling.
- Tail process. More than 100 nm in length. A hollow cylindrical rod runs through the inside, and on the outside it is surrounded by a sheath capable of contraction (containing ATP and calcium ions).
- Basal apparatus. The distal part with a hexagonal plate, spikes, and extending long fibers (fibrils) — all of this is necessary for attachment to the bacterium. It also contains the enzyme lysozyme for local dissolution of the cell wall.
Life cycle of virulent bacteriophages
Virulent phages cause a productive infection that inevitably ends in the death of the bacterium. The process, taking 20–40 minutes, is divided into several stages:
- Adsorption. The phage attaches via fibrils to specific cell receptors (lipopolysaccharides, teichoic acids, pili).
- Injection (penetration). The tail sheath contracts, lysozyme melts a section of the wall, and the hollow rod punctures the membranes. Through it, the phage genome is injected into the cytoplasm. Meanwhile, the protein «shadow» of the phage (capsid) remains outside.
- Reproduction. The injected DNA or RNS blocks the synthesis of the cell's own substances. The bacterium begins to produce virus components.
- Assembly (self-assembly). Empty heads are filled with nucleic acid, after which tail processes attach to them.
- Release. Due to changes in osmotic pressure and the action of phage lysozyme, the bacterial wall is destroyed, and 200–300 new virions are released.
Specificity and medical application
The interaction between phage and bacterium is strictly specific. Based on this feature, polyvalent (infect related species), monovalent (only one species), and typological (individual variants of a single species) phages are distinguished.
High specificity has found application in three areas of medicine:
- Diagnostics (phage typing): allows precise identification of the species or type of pathogen based on its susceptibility to reference diagnostic phages.
- Therapy: oral or local administration of preparations for treating bacterial infections (e.g., in purulent surgery, cholera, dysentery). The evaluation of therapeutic efficacy is characterized as moderate.
- Prophylaxis: use during epidemic outbreaks to block the spread of infection.
Phage preparations are produced by cultivating bacteria with phages and subsequently isolating the filtrate, the activity of which is titered on sensitive cultures.
Briefly: answers to topical questions
How does the life cycle of a virulent bacteriophage differ from a temperate one?
The life cycle of virulent and temperate bacteriophages differs in the possible pathways of infection development.
| Characteristic | Virulent bacteriophage | Temperate bacteriophage |
|---|---|---|
| Type of infection | Productive only (lytic cycle) | Productive or integrative (lysogenic cycle) |
| Interaction with the genome | Does not integrate | Phage DNA integrates into the bacterial chromosome (forms a prophage) |
| Outcome for the cell | Obligate lysis (death) of the bacterium | Lysis (in productive type) or coexistence and division along with the prophage |
What types of nucleic acids can form the genome of bacteriophages?
The genome of bacteriophages can be formed by various variants of DNA and RNA molecules.
- DNA-containing — the predominant type, most commonly containing double-stranded DNA closed in a ring. Single-stranded forms are also found.
- RNA-containing — contain RNA molecules (e.g., plus-RNA).
Phage nucleic acids can have a single-stranded or double-stranded structure, and can be linear or circular in shape.
What is phage (lysogenic) conversion and how does it affect the properties of bacteria?
Phage (lysogenic) conversion is the acquisition of new biological properties by a bacterial cell under the influence of the integrated prophage genome.
It can alter:
- morphological properties;
- cultural properties;
- biochemical (enzymatic) properties;
- antigenic properties.
For example, Corynebacterium diphtheriae produces diphtheria exotoxin only in the presence of a specific prophage. Non-toxigenic streptococcal strains can acquire the ability to produce erythrogenic toxins when the corresponding genes are transferred by specific bacteriophages.
The degrees of phage specificity are easy to remember by the acronym PMT: Polyvalent, Monovalent, Typological (from the broadest spectrum to the narrowest).
Class and exam questions
What happens during the abortive type of interaction?
In the abortive type, the phage penetrates the bacterium, but phage progeny is not formed for some reason. As a result, the bacterial cell survives.
How does a bacteriophage destroy the cell wall upon penetration?
The distal part of the tail process contains the enzyme lysozyme. Upon contact, it locally dissolves the peptidoglycan of the bacterial cell wall, allowing the rod to puncture the membranes.
How stable are bacteriophages in the external environment?
They are significantly more resistant than most human viruses. Phages tolerate low temperatures and drying very well, but are rapidly killed by boiling, formalin, acids, and radiation.
What else to study on this topic
- Mechanisms of penetration of small cubic and filamentous phages
- Genetic apparatus of bacteriophages: variants of nucleic acid structure
- Antigenic structure of phages and the principle of division into serotypes
- Features of the integrative type of interaction (lysogeny)
- Methods of titration and evaluation of phage preparation activity
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