Arbitrium

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Arbitrium is a viral peptide produced by bacteriophages to communicate with each other and decide host cell fate. [1] 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.

Contents

Discovery

Arbitrium was first observed by a team led by Rotem Sorek, a microbial geneticist at the Weizmann Institute of Science in Israel. [2] [3] They were studying communication in Bacillus subtilis bacteria - in particular, how bacteria infected with phages warn nearby uninfected bacteria about the presence of these viruses. They found that the phages (strain phi3T) communicated with each other to co-ordinate their infection. [1] Additionally, they found similarities between the human innate immune system and the bacterial defense system against phages. It appears that components of the immune system originated from the bacterial defense system. [4]

Mechanism

When a temperate phages infects a bacterium, it may enter either the lytic or the lysogenic pathway. The lytic pathway causes the host to produce and release progeny virions, usually killing it in the process. The lysogenic pathway involves the virus inserting itself into the bacterium's chromosome. At a later stage, the viral genome is activated, and it continues along the lytic pathway of producing and releasing progeny virions.

Arbitrium is used by at least some phages to judge how common fresh hosts are. Each infection causes the production of some arbitrium, and the remaining phages gauge the concentration of arbitrium around them. If the arbitrium concentration is too high, it may indicate that uninfected hosts are running out. The viruses then switch from lysis to lysogeny, so as to not deplete all available hosts. [1]

According to a team led by Alberto Marina at the Biomedical Institute of Valencia in Spain, also studying the Bacillus subtilis/ SPbeta phage system, arbitrium (AimP) binds to the AimX transcription factor AimR, and suppresses the activity of AimX, a negative regulator of lysogeny. [5] [6] [7] Marina has also shown in the same system that the virus's arbitrium receptor interacts not only with bacterial genes that help it reproduce, but also with several other stretches of DNA. He has suggested that arbitrium signals may be able to alter the activity of important bacterial genes. [1]

More recently, another team at the Sorek lab, headed by Avigail Stokar-Avihail and Nitzan Tal, has shown similar systems in other species of Bacillus bacteria, the pathogenic species Bacillus anthracis , Bacillus cereus , and Bacillus thuringiensis . [8] They speculate that "the occurrence of peptide-based communication systems among phages more broadly remains to be explored." [8]

Regulation

Arbitrium peptide AimR bound to a DNA Operator in SPbeta Phages.png
Arbitrium peptide

The arbitrium protein is synthesized by three genes: aimP, responsible for encoding the arbitrium peptide, aimR, responsible for encoding transcription factors that bind to aimP, and aimX, which produces non-coding RNA that suppresses lysogeny. The structure of aimR complex is still unknown. As a result lysis is induced by a mechanism that we still are unaware of. The AimP gene codes for a 43 amino acid (aa) peptide, which matures into a 6 amino acid (aa) active form. The mature protein is transported to neighboring bacteria using the oligopeptide permease (OPP) transporter channel. The OPP transport channel is capable of transporting peptides inside the bacteria cell with no specific size, composition, charge, or sequence. [9] Once inside, the mature AimP binds to the AimR receptor and regulates its activity. As a result, AimR loses its DNA-binding ability. AimX, whose expression is promoted by AimR, is also thus suppressed. [10] [6] [11]

In the early stages of infection the number of active phages is quite low. At this point, the arbitrium peptide is not yet present and AimR activates aimX expression. This would then promote the lytic cycle of the phage. Once the phage has replicated multiple times, AimP builds up in the medium. The concentration of the mature AimP peptide increases until it reaches the threshold level required to bind to the AimR receptor. If and when this occurs, AimR stops activating aimX expression, causing the stimulation of the lysogenic cycle as well as the integration of the prophage into the bacterial chromosome. This then keeps eradication of the bacterial population by the phage from occurring. The arbitrium communication system thus allows infecting phages to decide the cell fate. [12] [5]

Applications

Sorek has suggested that since human viruses like HIV and herpes simplex can cause active and latent infections, they might be using an arbitrium-like system to communicate. In this case, that analogue could be used to suppress infections by making the viruses completely latent. [1] [2] Prof. Martha Clokie, of the University of Leicester, has hailed the discovery of viral communication as 'transformative'. [2]

See also

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 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">Prophage</span> Bacteriophage genome that is integrated into a bacterial cell

A prophage is a bacteriophage genome that is integrated into the circular bacterial chromosome or exists as an extrachromosomal plasmid within the bacterial cell. 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.

<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.

<span class="mw-page-title-main">Lytic cycle</span> Cycle of viral reproduction

The lytic cycle is one of the two cycles of viral reproduction, the other being the lysogenic cycle. The lytic cycle results in the destruction of the infected cell and its membrane. Bacteriophages that only use the lytic cycle are called virulent phages.

<span class="mw-page-title-main">Viral plaque</span> Visible structure formed by virus propagation within a cell culture

A viral plaque is a visible structure formed after introducing a viral sample to a cell culture grown on some nutrient medium. The virus will replicate and spread, generating regions of cell destruction known as plaques. For example, Vero cell or other tissue cultures may be used to investigate an influenza virus or coronavirus, while various bacterial cultures would be used for bacteriophages.

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.

<span class="mw-page-title-main">T7 phage</span> Species of virus

Bacteriophage T7 is a bacteriophage, a virus that infects bacteria. It infects most strains of Escherichia coli and relies on these hosts to propagate. Bacteriophage T7 has a lytic life cycle, meaning that it destroys the cell it infects. It also possesses several properties that make it an ideal phage for experimentation: its purification and concentration have produced consistent values in chemical analyses; it can be rendered noninfectious by exposure to UV light; and it can be used in phage display to clone RNA binding proteins.

<span class="mw-page-title-main">Cyanophage</span> Virus that infects cyanobacteria

Cyanophages are viruses that infect cyanobacteria, also known as Cyanophyta or blue-green algae. Cyanobacteria are a phylum of bacteria that obtain their energy through the process of photosynthesis. Although cyanobacteria metabolize photoautotrophically like eukaryotic plants, they have prokaryotic cell structure. Cyanophages can be found in both freshwater and marine environments. Marine and freshwater cyanophages have icosahedral heads, which contain double-stranded DNA, attached to a tail by connector proteins. The size of the head and tail vary among species of cyanophages. Cyanophages infect a wide range of cyanobacteria and are key regulators of the cyanobacterial populations in aquatic environments, and may aid in the prevention of cyanobacterial blooms in freshwater and marine ecosystems. These blooms can pose a danger to humans and other animals, particularly in eutrophic freshwater lakes. Infection by these viruses is highly prevalent in cells belonging to Synechococcus spp. in marine environments, where up to 5% of cells belonging to marine cyanobacterial cells have been reported to contain mature phage particles.

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">Lysin</span>

Lysins, also known as endolysins or murein hydrolases, are hydrolytic enzymes produced by bacteriophages in order to cleave the host's cell wall during the final stage of the lytic cycle. Lysins are highly evolved enzymes that are able to target one of the five bonds in peptidoglycan (murein), the main component of bacterial cell walls, which allows the release of progeny virions from the lysed cell. Cell-wall-containing Archaea are also lysed by specialized pseudomurein-cleaving lysins, while most archaeal viruses employ alternative mechanisms. Similarly, not all bacteriophages synthesize lysins: some small single-stranded DNA and RNA phages produce membrane proteins that activate the host's autolytic mechanisms such as autolysins.

<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">Phage typing</span>

Phage typing is a phenotypic method that uses bacteriophages for detecting and identifying single strains of bacteria. Phages are viruses that infect bacteria and may lead to bacterial cell lysis. The bacterial strain is assigned a type based on its lysis pattern. Phage typing was used to trace the source of infectious outbreaks throughout the 1900s, but it has been replaced by genotypic methods such as whole genome sequencing for epidemiological characterization.

<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.

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.

<span class="mw-page-title-main">CII protein</span> InterPro Family

cII or transcriptional activator II is a DNA-binding protein and important transcription factor in the life cycle of lambda phage. It is encoded in the lambda phage genome by the 291 base pair cII gene. cII plays a key role in determining whether the bacteriophage will incorporate its genome into its host and lie dormant (lysogeny), or replicate and kill the host (lysis).

<span class="mw-page-title-main">Kill the Winner hypothesis</span> Microbiological population model hypothesis

The "Kill the Winner" hypothesis (KtW) is an ecological model of population growth involving prokaryotes, viruses and protozoans that links trophic interactions to biogeochemistry. The model is related to the Lotka–Volterra equations. It assumes that prokaryotes adopt one of two strategies when competing for limited resources: priority is either given to population growth ("winners") or survival ("defenders"). As "winners" become more abundant and active in their environment, their contact with host-specific viruses increases, making them more susceptible to viral infection and lysis. Thus, viruses moderate the population size of "winners" and allow multiple species to coexist. Current understanding of KtW primarily stems from studies of lytic viruses and their host populations.

<span class="mw-page-title-main">Integration host factor</span>

The integration host factor (IHF) is a bacterial DNA binding protein complex that facilitates genetic recombination, replication, and transcription by binding to specific DNA sequences and bending the DNA. It also facilitates the integration of foreign DNA into the host genome. It is a heterodimeric complex composed of two homologous subunits IHFalpha and IHFbeta.

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