Arbitrium

Arbitrium is a viral peptide produced by bacteriophages to communicate with each other and decide cell fates.[1] It is six amino acids(aa) long, also referred to as a hexapeptide, and is produced when a phage infects a bacterial host. Amino acids (aa) are composed molecules that form a protein. If a protein is broken down or digested, it leaves behind amino acids (aa). It signals to other phages that a host has been infected. Arbitrium is made up of three genes which are: aimP, it is responsible for encoding the arbitrium peptide. There is also aimR, the structure of aimR complex is still unknown, it is responsible for encoding transcription factors that happen to bind to aimP. Then theres aimX, it is responsible for producing non-coding RNA which brings to bear a negative regulatory effect on lysogeny. As a result lysis is induced by a mechanism that we still are unaware of. The AimP is made up into 43 amino acid(aa) peptide which is a product of the bacterial cell and goes into the medium. Evidently the peptide of 43 amino acids(aa) matures into a 6 amino acid(aa) AimP. The mature AimP 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 . Once inside, the mature AimP binds to the AimR, specifically the AimP to the AimR receptor. Once bound the DNA regulatory activity is being controlled. AimX expression is promoted to AimR since they are transcriptional factors and in their apo peptide-free form. Before complete infection the number of active phages is at a minimum. Due to the fact that the arbitrium peptide isn't present and AimR is needed in order to activate aimX expression. This would then promote the lytic cycle of the phage. Once phage has replicated multiple times AimP builds up in the medium. This increases the concentration inside of the mature AimP peptide. The intracellular concentration stops increasing once it reaches the threshold level which is required to bind to it's cognate AimR receptor. If and when this occurs AimR wont activate 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 is what allows infecting phages to decide the cell fate of either lytic or lysogenic cycle.

In Bacillus

Arbitrium is a peptide communication system used by bacterial phages, like Bacillus, which is gram-positive. It plays a key role during infection of the Bacillus host cells11-14 during the lysis-lysogeny decisions. The reason why arbitrium is necessary is because it is the communication system of lysis-lysogeny. In order to successfully transcribe the lysogeny negative regulator gene aimX, arbitriums hexapeptide, 6 amino acids(aa) long, must bind to the AimR receptor. The structure of the AimR complex is still unknown, this impedes a deeper understanding between the lytic and lysogenic cycles in the arbitrium system. When the Bacillus host cells are infected, precursors are produced to signal the peptides which are encoded by the gene aimP. The hexapeptide, 6 amino acids(aa) long, must mature by secreting the premature peptides to the outside environment and cleaved by the bacterial outside proteases. The secreted premature peptides are now mature peptides (MP) and secrete into the host cell by a transporter called oligopeptide permease. The reason why the premature peptides need to mature into mature peptides (MP) is due to their function. The mature peptides (MP) are capable of controlling virus replication. As well as transmission, pathogenicity, and host response. All these factors lead to determining patient outcome . They then bind to the AimR receptor which happens to function as a transcription factor. As a result, DNA-binding activity is lost in the AimR peptide-bound. Consequently, this sends a signal to the phage integration in the Bacillus genome in form of a prophage. Inside the prophage is all the all the genetic material of the bacteriophage, in our case Bacillus. The bacteriophages genomes will integrate into the host genome.

Arbitrium peptide

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 .

Mechanism

Many phages, known as temperate phages, when they infect a bacterium, may enter either the lytic or the lysogenic pathway. The lytic pathway causes the host to produce and release progeny virion, 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 decide 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.[4][5][6] 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 Bacilllus bacteria, the pathogenic species Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis. [7] They speculate that "the occurrence of peptide-based communication systems among phages more broadly remains to be explored."[7]

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

References
  1. Dolgin, Elie (2019). "The secret social lives of viruses". Nature. 570 (7761): 290–292. doi:10.1038/d41586-019-01880-6. PMID 31213694.
  2. Callaway, Ewen (2017). "Do you speak virus? Phages caught sending chemical messages". Nature. doi:10.1038/nature.2017.21313.
  3. Erez, Zohar; Steinberger-Levy, Ida; Shamir, Maya; Doron, Shany; Stokar-Avihail, Avigail; Peleg, Yoav; Melamed, Sarah; Leavitt, Azita; Savidor, Alon; Albeck, Shira; Amitai, Gil; Sorek, Rotem (2017-01-26). "Communication between viruses guides lysis–lysogeny decisions". Nature. 541 (7638): 488–493. doi:10.1038/nature21049. ISSN 0028-0836. PMC 5378303. PMID 28099413.
  4. Gallego del Sol, Francisca; Penadés, José R.; Marina, Alberto (2019). "Deciphering the Molecular Mechanism Underpinning Phage Arbitrium Communication Systems". Molecular Cell. 74 (1): 59–72. doi:10.1016/j.molcel.2019.01.025. PMC 6458997. PMID 30745087.
  5. Guan, Zeyuan; et al. (2019). "Structural insights into DNA recognition by AimR of the arbitrium communication system in the SPbeta phage" (PDF). Cell Discovery. 5: 29–. doi:10.1038/s41421-019-0101-2. PMC 6536502. PMID 31149347.
  6. Dou C, Xiong J, Gu Y, Yin K, Wang J, Hu Y, Zhou D, Fu X, Qi S, Zhu X, Yao S. Structural and functional insights into the regulation of the lysis–lysogeny decision in viral communities. Nature microbiology. 2018 Nov;3(11):1285.
  7. Stokar-Avihail A, Tal N, Erez Z, Lopatina A, Sorek R. Widespread Utilization of Peptide Communication in Phages Infecting Soil and Pathogenic Bacteria. Cell host & microbe. 2019 May 8;25(5):746-55.
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