Prophage

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Formation of a prophage Prophage SVG.svg
Formation of a prophage

A prophage is a bacteriophage (often shortened to "phage") genome that is integrated into the circular bacterial chromosome or exists as an extrachromosomal plasmid within the bacterial cell. [1] Integration of prophages into the bacterial host is the characteristic step of the lysogenic cycle of temperate phages. Prophages remain latent in the genome through multiple cell divisions until activation by an external factor, such as UV light, leading to production of new phage particles that will lyse the cell and spread. As ubiquitous mobile genetic elements, prophages play important roles in bacterial genetics and evolution, such as in the acquisition of virulence factors.

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Prophage induction

Upon detection of host cell damage by UV light or certain chemicals, the prophage is excised from the bacterial chromosome in a process called prophage induction. After induction, viral replication begins via the lytic cycle. In the lytic cycle, the virus commandeers the cell's reproductive machinery. The cell may fill with new viruses until it lyses or bursts, or it may release the new viruses one at a time in an exocytotic process. The period from infection to lysis is termed the latent period. A virus following a lytic cycle is called a virulent virus. Prophages are important agents of horizontal gene transfer, and are considered part of the mobilome. Genes are transferred via transduction as the prophage genome is imperfectly excised from the host chromosome and integrated into a new host (specialized transduction) or as fragments of host DNA are packaged into the phage particles and introduced into a new host (generalized transduction). [2] All families of bacterial viruses that have circular (single-stranded or double-stranded) DNA genomes or replicate their genomes through rolling circle replication (e.g., Caudovirales) have temperate members. [3]

Zygotic induction

Zygotic induction occurs when a bacterial cell carrying the DNA of a bacterial virus transfers its own DNA along with the viral DNA (prophage) into the new host cell. This has the effect of causing the host cell to break apart. [4] The DNA of the bacterial cell is silenced before entry into the cell by a repressor protein which is encoded for by the prophage. Upon the transfer of the bacterial cell's DNA into the host cell, the repressor protein is no longer encoded for, and the bacterial cell's original DNA is then turned on in the host cell. This mechanism eventually will lead to the release of the virus as the host cell splits open and the viral DNA is able to spread. [4] This new discovery provided key insights into bacterial conjugation and contributed to the early repression model of gene regulation, which provided an explanation as to how the lac operon and λ bacteriophage genes are negatively regulated. [5]

Prophage reactivation

Bacteriophage λ is able to undergo a type of recombinational repair called prophage reactivation. [5] [6] Prophage reactivation can occur by recombination between a UV-damaged infecting phage λ chromosome and a homologous phage genome integrated into the bacterial DNA and existing in a prophage state. Prophage reactivation in the case of phage λ appears to be an accurate recombinational repair process that is mediated by the recA+ and red+ gene products.[ citation needed ]

Cost/benefit to the host

Lysis of host cells during prophage induction can cause the collapse of a microbial population. [7] [8] On the other hand, induction, transduction and superinfection exclusion mechanisms confer many beneficial functions to the host. Induction of prophages allows hosts to compete in the microbial ecology by infecting and lysing susceptible bacteria. [9] Phages also enable the host to pick up and integrate antibiotic resistance genes from nearby cells. [8] [9] [7] [10] Additionally, phages can enable the host to acquire virulence and pathogenicity genes. [8] [10] Modulation of biofilm formation is also affected by infection by lysogenic phages. [10] Superinfection exclusion, or protection against infection by multiple phages, can be conferred by prophage integration. [11] Additionally, phage-mediated recombination mechanisms may remodel the host chromosome and provide new ways for cells to regulate metabolism and gene expression, such as those involved in sporulation and competence. [10] [12]

Applications

Prophages can tell researchers a lot about the relationship between a bacterium and a host. [13] With data from more nonpathogenic bacteria, researchers will be able to gather evidence as to whether or not prophages contribute to the survival value of the host. Prophage genomics has the potential to lead to ecological adaptations of the relationships between bacteria. [13] Another important area of interest is the control of prophage gene expression with many of the lysogenic conversion genes (gene conversion) being tightly regulated. [14] This process is capable of converting non-pathogenic bacteria into pathogenic bacteria that can now produce harmful toxins [14] such as in staph infections. Since the specific mechanisms of prophage are not yet detailed, this research could provide the community with this tool for future research. [13]

Economic impact

Exotoxins encoded by prophages cause pathogenic outcomes in agriculture and aquaculture. [15]

Related Research Articles

<span class="mw-page-title-main">Bacteriophage</span> Virus that infects and replicates within bacteria

A bacteriophage, also known informally as a phage, is a virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν, meaning "to devour". Bacteriophages are composed of proteins that encapsulate a DNA or RNA genome, and may have structures that are either simple or elaborate. Their genomes may encode as few as four genes and as many as hundreds of genes. Phages replicate within the bacterium following the injection of their genome into its cytoplasm.

<span class="mw-page-title-main">Lambda phage</span> Bacteriophage that infects Escherichia coli

Enterobacteria phage λ is a bacterial virus, or bacteriophage, that infects the bacterial species Escherichia coli. It was discovered by Esther Lederberg in 1950. The wild type of this virus has a temperate life cycle that allows it to either reside within the genome of its host through lysogeny or enter into a lytic phase, during which it kills and lyses the cell to produce offspring. Lambda strains, mutated at specific sites, are unable to lysogenize cells; instead, they grow and enter the lytic cycle after superinfecting an already lysogenized cell.

A provirus is a virus genome that is integrated into the DNA of a host cell. In the case of bacterial viruses (bacteriophages), proviruses are often referred to as prophages. However, proviruses are distinctly different from prophages and these terms should not be used interchangeably. Unlike prophages, proviruses do not excise themselves from the host genome when the host cell is stressed.

A lysogen or lysogenic bacterium is a bacterial cell which can produce and transfer the ability to produce a phage. A prophage is either integrated into the host bacteria's chromosome or more rarely exists as a stable plasmid within the host cell. The prophage expresses gene(s) that repress the phage's lytic action, until this repression is disrupted. Currently a variety of studies are being conducted to see whether other genes are active during lysogeny, examples of which include phage-encoded tRNA and virulence genes.

<span class="mw-page-title-main">Transduction (genetics)</span> Transfer process in genetics

Transduction is the process by which foreign DNA is introduced into a cell by a virus or viral vector. An example is the viral transfer of DNA from one bacterium to another and hence an example of horizontal gene transfer. Transduction does not require physical contact between the cell donating the DNA and the cell receiving the DNA, and it is DNase resistant. Transduction is a common tool used by molecular biologists to stably introduce a foreign gene into a host cell's genome.

<i>Escherichia virus T4</i> Species of bacteriophage

Escherichia virus T4 is a species of bacteriophages that infect Escherichia coli bacteria. It is a double-stranded DNA virus in the subfamily Tevenvirinae from the family Myoviridae. T4 is capable of undergoing only a lytic life cycle and not the lysogenic life cycle. The species was formerly named T-even bacteriophage, a name which also encompasses, among other strains, Enterobacteria phage T2, Enterobacteria phage T4 and Enterobacteria phage T6.

In virology, temperate refers to the ability of some bacteriophages to display a lysogenic life cycle. Many temperate phages can integrate their genomes into their host bacterium's chromosome, together becoming a lysogen as the phage genome becomes a prophage. A temperate phage is also able to undergo a productive, typically lytic life cycle, where the prophage is expressed, replicates the phage genome, and produces phage progeny, which then leave the bacterium. With phage the term virulent is often used as an antonym to temperate, but more strictly a virulent phage is one that has lost its ability to display lysogeny through mutation rather than a phage lineage with no genetic potential to ever display lysogeny.

<span class="mw-page-title-main">Lysogenic cycle</span> Process of virus reproduction

Lysogeny, or the lysogenic cycle, is one of two cycles of viral reproduction. Lysogeny is characterized by integration of the bacteriophage nucleic acid into the host bacterium's genome or formation of a circular replicon in the bacterial cytoplasm. In this condition the bacterium continues to live and reproduce normally, while the bacteriophage lies in a dormant state in the host cell. The genetic material of the bacteriophage, called a prophage, can be transmitted to daughter cells at each subsequent cell division, and later events can release it, causing proliferation of new phages via the lytic cycle.

Salmonella virus P22 is a bacteriophage in the Podoviridae family that infects Salmonella typhimurium. Like many phages, it has been used in molecular biology to induce mutations in cultured bacteria and to introduce foreign genetic material. P22 has been used in generalized transduction and is an important tool for investigating Salmonella genetics.

Allan McCulloch Campbell was an American microbiologist and geneticist and the Barbara Kimball Browning Professor Emeritus in the Department of Biology at Stanford University. His pioneering work on Lambda phage helped to advance molecular biology in the late 20th century. An important collaborator and member of his laboratory at Stanford University was biochemist Alice del Campillo Campbell, his wife.

<span class="mw-page-title-main">Esther Lederberg</span> American microbiologist (1922–2006)

Esther Miriam Zimmer Lederberg was an American microbiologist and a pioneer of bacterial genetics. She discovered the bacterial virus lambda phage and the bacterial fertility factor F, devised the first implementation of replica plating, and furthered the understanding of the transfer of genes between bacteria by specialized transduction.

P1 is a temperate bacteriophage that infects Escherichia coli and some other bacteria. When undergoing a lysogenic cycle the phage genome exists as a plasmid in the bacterium unlike other phages that integrate into the host DNA. P1 has an icosahedral head containing the DNA attached to a contractile tail with six tail fibers. The P1 phage has gained research interest because it can be used to transfer DNA from one bacterial cell to another in a process known as transduction. As it replicates during its lytic cycle it captures fragments of the host chromosome. If the resulting viral particles are used to infect a different host the captured DNA fragments can be integrated into the new host's genome. This method of in vivo genetic engineering was widely used for many years and is still used today, though to a lesser extent. P1 can also be used to create the P1-derived artificial chromosome cloning vector which can carry relatively large fragments of DNA. P1 encodes a site-specific recombinase, Cre, that is widely used to carry out cell-specific or time-specific DNA recombination by flanking the target DNA with loxP sites.

<span class="mw-page-title-main">Mobilome</span>

The mobilome is the entire set of mobile genetic elements in a genome. Mobilomes are found in eukaryotes, prokaryotes, and viruses. The compositions of mobilomes differ among lineages of life, with transposable elements being the major mobile elements in eukaryotes, and plasmids and prophages being the major types in prokaryotes. Virophages contribute to the viral mobilome.

<span class="mw-page-title-main">Corynebacteriophage</span> Virus of bacteria

A corynebacteriophage is a DNA-containing bacteriophage specific for bacteria of genus Corynebacterium as its host. Corynebacterium diphtheriae virus strain Corynebacterium diphtheriae phage introduces toxigenicity into strains of Corynebacterium diphtheriae as it encodes diphtheria toxin, it has subtypes beta c and beta vir. According to proposed taxonomic classification, corynephages β and ω are unclassified members of the genus Lambdavirus, family Siphoviridae.

<span class="mw-page-title-main">Bacteriophage P2</span> Species of virus

Bacteriophage P2, scientific name Escherichia virus P2, is a temperate phage that infects E. coli. It is a tailed virus with a contractile sheath and is thus classified in the genus Peduovirus, subfamily Peduovirinae, family Myoviridae within order Caudovirales. This genus of viruses includes many P2-like phages as well as the satellite phage P4.

Zygotic induction occurs when a bacterial cell carrying the silenced DNA of a bacterial virus in its chromosome transfers the viral DNA along with its own DNA to another bacterial cell lacking the virus, causing the recipient of the DNA to break open. In the donor cell, a repressor protein encoded by the prophage keeps the viral genes turned off so that virus is not produced. When DNA is transferred to the recipient cell by conjugation, the viral genes in the transferred DNA are immediately turned on because the recipient cell lacks the repressor. As a result, many virus are made in the recipient cell, and lysis eventually occurs to release the new virus.

SaPIs are a family of ~15 kb mobile genetic elements resident in the genomes of the vast majority of S. aureus strains. Much like bacteriophages, SaPIs can be transferred to uninfected cells and integrate into the host chromosome. Unlike the bacterial viruses, however, integrated SaPIs are mobilized by host infection with "helper" bacteriophages. SaPIs are used by the host bacteria to co-opt the phage reproduction cycle for their own genetic transduction and also inhibit phage reproduction in the process.

The CTXφ bacteriophage is a filamentous bacteriophage. It is a positive-strand DNA virus with single-stranded DNA (ssDNA).

Bacteriophage T12 is a bacteriophage that infects Streptococcus pyogenes bacteria. It is a proposed species of the family Siphoviridae in the order Caudovirales also known as tailed viruses. It converts a harmless strain of bacteria into a virulent strain. It carries the speA gene which codes for erythrogenic toxin A. speA is also known as streptococcal pyogenic exotoxin A, scarlet fever toxin A, or even scarlatinal toxin. Note that the name of the gene "speA" is italicized; the name of the toxin "speA" is not italicized. Erythrogenic toxin A converts a harmless, non-virulent strain of Streptococcus pyogenes to a virulent strain through lysogeny, a life cycle which is characterized by the ability of the genome to become a part of the host cell and be stably maintained there for generations. Phages with a lysogenic life cycle are also called temperate phages. Bacteriophage T12, proposed member of family Siphoviridae including related speA-carrying bacteriophages, is also a prototypic phage for all the speA-carrying phages of Streptococcus pyogenes, meaning that its genome is the prototype for the genomes of all such phages of S. pyogenes. It is the main suspect as the cause of scarlet fever, an infectious disease that affects small children.

Arbitrium is a viral peptide produced by bacteriophages to communicate with each other and decide host cell fate. It is six amino acids(aa) long, and so is also referred to as a hexapeptide. It is produced when a phage infects a bacterial host. and signals to other phages that the host has been infected.

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See also