Prophages: Infection, Transmission & Diseases

Prophage is the name given to the phage DNA of temperate bacteriophages when it is present in the bacterial host cell. Bacteriophages were discovered by Félix Hubert d’Hérelle in 1917. They are viruses that have adapted to specific bacteria. Later research distinguished between the lytic phage with high virulence and the temperate phage with silent prophage and lysogenic cycle.

What are prophages?

The prophage of the temperate bacteriophage can be present as a plasmid in the host cell or integrated into the bacterial DNA. For this, the temperate phage must adopt the lysogenic cycle upon injection of the phage DNA. A distinction is made between the lytic cycle and the lysogenic cycle. While the lytic cycle causes rapid replication and subsequent lysis of the host cell after the injection of the genetic material, in the lysogenic cycle, repressor genes of the phage are injected into the host cell to suppress the lytic cycle, i.e. the rapid dissolution of the cell. The temperate phage can switch between lytic and lysogenic cycles depending on the environmental condition present. The lytic cycle refers to the conventional approach of the phage genes within the host cell. There is rapid replication within the host cell after injection of the viral DNA. After the capsid and tail fiber proteins have been replicated in addition to the viral DNA and numerous new viral particles have been assembled from the individual parts, the cell wall of the host cell is disintegrated by lysozyme. The dissolution of the cell wall releases the new phages and they can now inject their DNA into further bacterial cells. This process is completed in about one hour. Due to the high number of new viral particles, this process is called “virulent form”. Since the host cell wall is destroyed by lysozyme, the term “lytic cycle” is used. In the temperate phage, rapid replication and subsequent lysis of the host cell does not necessarily come into effect. Depending on existing environmental factors, the temperate phage may alternate between lytic and lysogenic cycles. The lytic cycle can be suppressed by the injection of repressor genes and the lysogenic cycle can begin indefinitely. In the lysogenic cycle, the phage’s genetic material is inserted into the germ’s genetic material and can persist here for an indefinite time. The injected genetic material is referred to as “still”, and defined as “prophage”. The prophage can reside as a plasmid in the cytoplasm of the host cell or be integrated into the genetic material of the bacterium. The integration of the viral genetic material requires a high degree of specialization. The genetic material of temperate phages can only be attached to specific positions of bacterial DNA. Conversely, the genetic material of individual temperate phage strains can always be identified at the same positions of the bacterial genome. Due to the successful adaptation, prophages become beneficiaries of bacterial cell division. During the division process of the host cell mitosis, the viral genome is passed on. Further transmission to other bacteria can occur by conjugation. Prophages can thus spread through entire bacterial strains by various transmission routes. Environmental influences such as UV light or certain chemicals can cause the prophage to switch back to the lytic cycle and to seek aggressive replication. Furthermore, the prophage also takes advantage of the transcription processes of the host cell: The injected repressor genes of the phage are recognized as DNA damage by certain enzymes of the bacterium and degraded. The degradation of the repressor genes has a self-destructive effect within the host cell. The lytic cycle can now no longer be suppressed and the prophage switches from the lysogenic state to aggressive replication, which ends with the subsequent dissolution of the bacterial cell wall.

Occurrence, distribution, and properties

Phages are highly specialized viruses that have adapted to individual bacterial strains. Thus, not every bacteriophage can access every bacterium. Propagation without the specific host cell is not possible for the bacteriophage. The strong specialization leads to the fact that bacteriophages are found in the same terrain as their host cells. The same is true to an even greater degree for prophages.Since prophages are not conventional viruses and merely present themselves as viral genetic material within the host organism, they cannot be found outside the assigned cells, if only by definition. In addition, it must be mentioned that bacteriophages have a number of (10 to the power of 30) in seawater alone, and thus there are more phages than living organisms on the entire planet. This contrasts with a vanishingly small number of nineteen officially researched bacteriophages, making it difficult to make an accurate statement about their occurrence.

Significance and function

Phage therapy was developed in the 1920s and is still used successfully in Eastern Europe to combat various infectious diseases. The advantages of phage therapy are obvious: bacteriophages damage only individual strains of bacteria while antibiotics have a general damaging effect on bacteria of the body. The discovery of penicillin in the 1940s led to massive antibiotic use in the West and, as a result, a cessation of phage research. The subsequent build-up of numerous antibiotic resistances in turn triggered increased interest in bacteriophages in the 1990s. However, the focus of phage therapy is on bacteriophages with aggressive virulence and exclusively lytic cycle, whereas temperate bacteriophages and prophages have played only a minor role to date.

Diseases and ailments

Some pathogens can only establish their virulence through symbiosis with prophages. Clostridium botulinum can produce the dreaded botulinum toxin only with the help of integrated phage DNA. Streptococcus pyogenes can only cause scarlet fever in combination with prophage DNA. Vibrio cholerae produces cholera only through special prophages. This also shows the importance of phages for human medicine. Entire bacterial strains could lose their pathogenic potential if the responsible prophages could be specifically eliminated.