A virus infects a bacterial cell by first attaching to the bacterial cell wall by its tail. In coliphages the tail is a complex protein structure consisting of a hollow contractile sheath, with a plate at the base that contains long protein fibers. The tail fibers fix the base plate to the specific receptor site on the bacterial cell wall, and the tail sheath contracts like a syringe, forcing the DNA that is inside the virus through the cell wall and cell membrane. The entire virus protein coat remains outside the bacterium.
The injected nucleic acid is the viral genetic material; it makes use of the bacterium's chemical energy and biosynthetic machinery to produce viral enzymes, as well as more phage nucleic acid. The viral proteins and nucleic acid molecules within the bacterial host assemble spontaneously into up to a hundred new phage particles. Eventually the bacterium lyses, releasing the particles. Lysis can be readily observed in bacteria growing on a solid medium, where groups of lysed cells appear as clear areas, or plaques.
Some DNA phages, called temperate phages, only lyse a small fraction of bacterial cells; in the remaining majority of the bacteria, the phage DNA becomes integrated into the bacterial chromosome and replicates along with it. In this state, known as lysogeny, the information contained in the viral nucleic acid is not expressed. A lysogenic bacterial culture can be treated with radiation or mutagens, inducing the cells to begin producing viruses and lyse. Lysogenic phages resemble bacterial genetic particles known as episomes. Incorporated phage genes are sometimes the source of the virulence of disease-causing bacteria.
The bacteriophage was discovered independently by the microbiologists F. W. Twort (1915) and Félix d'Hérelle (1917). The phages have been much used in the study of bacterial genetics and cellular control mechanisms largely because the bacterial hosts are so easily grown and infected with phage in the laboratory. Phages were also used in an attempt to destroy bacteria that cause epidemic diseases, but this approach was largely abandoned in the 1940s when antibacterial drugs became available. The possibility of "phage therapy" has recently attracted new interest among medical researchers, however, owing to the increasing threat posed by drug-resistant bacteria. In 2006 the Food and Drug Administration approved the use of bacteriophages that attack strains of Listeria as a food additive on ready-to-eat meat products.
Typically, bacteriophages consist of an outer protein hull enclosing genetic material. The genetic material can be ssRNA (single stranded RNA), dsRNA, ssDNA, or dsDNA between 5 and 500 kilo base pairs long with either circular or linear arrangement. Bacteriophages are much smaller than the bacteria they destroy - usually between 20 and 200 nm in size.
Phages are estimated to be the most widely distributed and diverse entities in the biosphere. Phages are ubiquitous and can be found in all reservoirs populated by bacterial hosts, such as soil or the intestines of animals. One of the densest natural sources for phages and other viruses is sea water, where up to 9×108 virions per milliliter have been found in microbial mats at the surface, and up to 70% of marine bacteria may be infected by phages.
They have been used for over 60 years as an alternative to antibiotics in the former Soviet Union and Eastern Europe. They are seen as a possible therapy against multi drug resistant strains of many bacteria.
|Caudovirales||Myoviridae||Non-enveloped, contractile tail||Linear dsDNA|
|Siphoviridae||Non-enveloped, long non-contractile tail||Linear dsDNA|
|Podoviridae||Non-enveloped, short noncontractile tail||Linear dsDNA|
|Tectiviridae||Non-enveloped, isometric||Linear dsDNA|
|Corticoviridae||Non-enveloped, isometric||Circular dsDNA|
|Lipothrixviridae||Enveloped, rod-shaped||Linear dsDNA|
|Plasmaviridae||Enveloped, pleomorphic||Circular dsDNA|
|Rudiviridae||Non-enveloped, rod-shaped||Linear dsDNA|
|Fuselloviridae||Non-enveloped, lemon-shaped||Circular dsDNA|
|Inoviridae||Non-enveloped, filamentous||Circular ssDNA|
|Microviridae||Non-enveloped, isometric||Circular ssDNA|
|Leviviridae||Non-enveloped, isometric||Linear ssRNA|
|Cystoviridae||Enveloped, spherical||Segmented dsRNA|
In contrast, the lysogenic cycle does not result in immediate lysing of the host cell. Those phages able to undergo lysogeny are known as temperate phages. Their viral genome will integrate with host DNA and replicate along with it fairly harmlessly, or may even become established as a plasmid. The virus remains dormant until host conditions deteriorate, perhaps due to depletion of nutrients, then the endogenous phages (known as prophages) become active. At this point they initiate the reproductive cycle resulting in lysis of the host cell. As the lysogenic cycle allows the host cell to continue to survive and reproduce, the virus is reproduced in all of the cell’s offspring.
Sometimes prophages may provide benefits to the host bacterium while they are dormant by adding new functions to the bacterial genome in a phenomenon called lysogenic conversion. A famous example is the conversion of a harmless strain of Vibrio cholerae by a phage into a highly virulent one, which causes cholera. This is why temperate phages are not suitable for phage therapy.
To enter a host cell, bacteriophages attach to specific receptors on the surface of bacteria, including lipopolysaccharides, teichoic acids, proteins or even flagella. This specificity means that a bacteriophage can only infect certain bacteria bearing receptors that they can bind to, which in turn determines the phage's host range. As phage virions do not move independently, they must rely on random encounters with the right receptors when in solution (blood, lymphatic circulation, irrigation, soil water etc.).
Complex bacteriophages use a syringe-like motion to inject their genetic material into the cell. After making contact with the appropriate receptor, the tail fibers bring the base plate closer to the surface of the cell. Once attached completely, the tail contracts, possibly with the help of ATP present in the tail (Prescott, 1993), injecting genetic material through the bacterial membrane.
Phages were discovered to be anti-bacterial agents and put to use as such soon after they were discovered, with varying success. However, antibiotics were discovered some years later and marketed widely, popular because of their broad spectrum; also easier to manufacture in bulk, store and prescribe. Hence development of phage therapy was largely abandoned in the West, but continued throughout 1940s in the former Soviet Union for treating bacterial infections, with widespread use including the soldiers in the Red Army - much of the literature being in Russian or Georgian, and unavailable for many years in the West. This has continued after the war, with widespread use continuing in Georgia and elsewhere in Eastern Europe. There is anecdotal evidence there, but no completed clinical trials in the US or Western Europe.
Bacteriophages have also been used in hydrological tracing and modelling in river systems especially where surface water and groundwater interactions occur. The use of phage is preferred to the more conventional dye marker because they are significantly less adsorbed when passing through ground-waters and they are readily detected at very low concentrations.