Bacteriophages (phages) are obligate intracellular viruses that specifically infect bacteria. They were discovered independently by two researchers, Frederick William Twort1at the University of London in 1915 and Félix d'Herelle2who confirmed the discovery and coined the term bacteriophage in 1917 and have been widely studied since then.
The phage has a very simple structure (Figure 1). Its genetic material is contained in a prism-shaped head surrounded by a protein capsid. This is connected to the extended hem (sometimes called the tail) by a neck or collar area.
The envelope forms a hollow tube through which viral DNA/RNA is injected into the host cell and is surrounded by protective envelope proteins. At the bottom of the envelope is the baseplate, to which are attached tail fibers (usually six) that facilitate attachment to the host cell.
Lytic vs Lysogenic: What's the Difference?
The lytic cycle, or virulent infection, involves a virus taking over a host cell and using it to produce its viral progeny, killing the host in the process. The lysogenic cycle, or non-virulent infection, involves the virus assimilating its genome with the host cell's genome to achieve replication without killing the host.
Illustration 1.Example of the structure of a bacteriophage.
In order to multiply, the phage must first enter the host cell. They bind with their tail fibers to specific receptors on the surface of the bacterial cell (adsorption) and create a hole, a process that is coordinated by the base plate in addition to attachment.3🇧🇷 A rigid tube is ejected from the shell and pierces a hole in the bacterial cell's membrane through which they inject their genetic material (DNA or RNA, double-stranded or single-stranded). They can then hijack the host cell's cellular machinery for their own replication when environmental conditions in a process are unfavorablelytic cycle🇧🇷 Alternatively, they can enter a quiescent state known as the lysogenic cycle inside the host cell when conditions are right.
In the lytic cycle (Figure 2), sometimes referred to as virulent infection, the infecting phage eventually kills the host cell to produce many of its own progeny. Immediately after injection into the host cell, the phage genome synthesizes starter proteins that degrade the host's DNA and allow the phage to take control of the cellular machinery.
What are the stages of the lytic cycle?
The lysis cycle consists of four phases:
- Attachment of fago
- invasion of bacterial cells
- The birth of a new phage
For more information on these steps, see our article:
Understanding the Lytic Cycle - what are the steps?
The phage then uses the host cell to synthesize the remaining proteins needed to build new phage particles. The heads and envelopes are assembled separately, the new genetic material packed into the head, and the new daughter phage particles constructed. During this process, host cells are gradually weakened by phage enzymes and eventually rupture, releasing an average of 100-200 new phage progeny into the environment.
Figure 2.Diagram of the stages of the lytic cycle of bacteriophage.
See the lytic cycle in actionhere.
The lysogenic cycle (Figure 3), sometimes referred to as a moderate or non-virulent infection, does not kill the host cell but uses it as a haven where it exists in a quiescent state. After injection of phage DNA into the host cell, it integrates into the host genome with the help of phage-encoded integrases, where it is called a prophage. The prophage genome is then passively replicated along with the host genome as the host cell divides while remaining there and not making the necessary proteins to produce offspring. Because the phage genome is generally comparatively small, bacterial hosts are usually left relatively unharmed by this process.
Figure 3.Diagram of the stages of the lysogenic cycle of bacteriophage.
Transition from lysogenic to lytic
When a prophage-containing bacterium is exposed to stressors such as ultraviolet light, nutrient-poor conditions, or chemicals such as mitomycin C, the prophage can spontaneously extract itself from the host genome and enter the lytic cycle in a process called induction.
However, this process is not perfect and the prophages can sometimes leave behind parts of their DNA or take parts of the host's DNA with them when they recirculate. When they infect a new host cell, they can transfer bacterial genes from one strain to another in a process called transduction. This is a method by which antibiotic resistance genes, genes encoding toxins and superantigens, and other virulence traits can spread in a bacterial population.
Recent work has shown that the transition between lytic and lysogenic infection also depends on the abundance of phages in an area, as they are able to produce and detect small peptides in a process similar to quorum sensing.4.
Bacterial immunity to phage infection
Not all bacteria are defenseless against phage attack, as they have an "immune system" that allows them to fight back.CRISPR-Cas, which is now synonymous with genetic modification, was first proposed by Francisco Mojica as a bacterial "adaptive immune system".5and independent of a group from the Université Paris-Sud6in 2005. The CRISPR locus is an array of short repeated sequences separated by spacers with unique sequences. These spacer sequences have been found to share homology with viral and plasmid DNA, including phage. When attacked by a phage not previously encountered, new spacers are added to one side of the CRISPR, making the CRISPR a chronological record of the phage encountered by the cell and its ancestors. In response to phage invasion, CRISPR sequences are transcribed and, in cooperation with Cas proteins, target and destroy phage sequences homologous to the spacer sequences.
Phages as tools in molecular biology and genetics
The lambda phage originally isolated fromEscherichia coli, is one of the best-studied phages and has formed the basis of many genetic tools. It has been said that using phage as a tool eventually led to the development of molecular biology as a discipline.7🇧🇷 In the 1950s, the ability of phages to recombine with host DNA was first used to manipulate the genomes ofsalmonellaSpecies and therefore the process oftransmissionwas born8🇧🇷 Since then it has been used as a vehicle to move genetic material between many organisms, including genetic manipulation by fungi.9and even human genes. That was thanks to the humble phagehuman insulinwas produced safely and inexpensively for the first time. It has also opened applications in high-throughput clone screening and nanomaterial development10,antibacterial food treatment, As adiagnostic tooland drug discovery and delivery systems11.
The ϕX174 phage became an unknowing pioneer in 1977 when, thanks to Fred Sanger and colleagues, it became the first organism to have its entire nucleotide sequence determined12.
Before Alexander Fleming discovered antibiotics in 1928, the phage was explored as a method of treating bacterial infections. In the post-antibiotics era, the practical broad spectrum activity of antibiotic treatment has led to the abandonment of phage therapy research in most organizations. However, in many countries of the former Soviet Union lacking Western antibiotics, research into phage therapies necessarily continued. With the growing global problems ofantibiotic resistancethe field of phage therapy has experienced an upswing in recent years. Although phages are capable of infecting and destroying bacteria, they have been used successfully to treat life-threatening infections13, their species and even strain specificity, and the potential for pre-existing immunity of some bacteria mean that phage treatment is currently not a trivial process and must be tailored to the individual infection. This makes it expensive and time consuming. Consequently, this is currently a last resort and much work is still needed in this area.
The phage family tree
With the increasing availability and accessibility of nucleotide sequencing, the number of phage genomes submitted to databases has exploded over the past two decades.14.
Phages are classified byInternational Committee on the Taxonomy of Viruses(ICTV), as of its 2017 update, there are 19 phage families infecting bacteria and archaea (Table 1), but as more samples from more remote areas are sequenced, this is likely to increase in the future.
For mobile users, scroll left and right to view the data in the table below.
|Myoviridae||Bare and contractible tail||dsDNA linear||Fago T4, Mu, PBSX, P1Puna-ähnlich, P2, I3, Bcep 1, Bcep 43, Bcep 78||6||41|
|Siphoviridae||Non-sheathed non-contractile tail (long)||dsDNA linear||λ groove, groove T5, phi, C2, L5, HK97, N1||11||100|
|Podoviridae||Non-Sheathed Non-Contractile Tail (Short)||dsDNA linear||Fago T7, Fago T3, Φ29, P22, P37||3||23|
|Ligamenvirale||Lipothrixviridae||Coiled, rod-shaped||dsDNA linear||Acid filamentous virus 1||3|
|Rudiviridae||Bare, rod-shaped||dsDNA linear||Rod-shaped virus Sulfolobus islandicus 1||1|
|not assigned||Ampullaviridae||Encased, bottle-shaped||dsDNA linear||1|
|Bicaudaviridae||Unwrapped, lemon-shaped||dsDNA circular||1|
|Clavaviridae||Bare, rod-shaped||dsDNA circular||1|
|Corticoviridae||Bare, isometric||dsDNA circular||1|
|Cystoviridae||encased, globular||segmented dsRNA||1|
|Fuselloviridae||Unwrapped, lemon-shaped||dsDNA circular||2|
|Globuloviridae||enveloped, isometric||dsDNA linear||1|
|Guttaviridae||Not enveloping, ovate||dsDNA circular||2|
|Inoviridae||Uncovered, threadlike||ssDNA Circular||M13||7|
|Leviviridae||Bare, isometric||ssRNA linear||MS2,Qβ||2|
|Microviridae||Bare, isometric||ssDNA Circular||ΦX174||2||6|
|Plasmaviridae||encased, pleomorphic||dsDNA circular||1|
|Tectiviridae||Bare, isometric||dsDNA linear||2|
Table 1.ICTV taxonomic classification of bacteriophages infecting bacteria and archaea.
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