arbitrium

Arbitrium was first observed by a team led by Rotem Sorek, a microbial geneticist at the Weizmann Institute of Science in Israel.{{cite journal |last1=Callaway |first1=Ewen |title=Do you speak virus? Phages caught sending chemical messages |journal=Nature |date=18 January 2017 |doi=10.1038/nature.2017.21313 |s2cid=90839014 }}{{cite journal | last1=Erez | first1=Zohar | last2=Steinberger-Levy | first2=Ida | last3=Shamir | first3=Maya | last4=Doron | first4=Shany | last5=Stokar-Avihail | first5=Avigail | last6=Peleg | first6=Yoav | last7=Melamed | first7=Sarah | last8=Leavitt | first8=Azita | last9=Savidor | first9=Alon | last10=Albeck | first10=Shira | last11=Amitai | first11=Gil | last12=Sorek | first12=Rotem | title=Communication between viruses guides lysis–lysogeny decisions | journal=Nature | volume=541 | issue=7638 | date=2017-01-26 | issn=0028-0836 | pmid=28099413 | pmc=5378303 | doi=10.1038/nature21049 | pages=488–493| bibcode=2017Natur.541..488E }} 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. 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.{{cite web | url=https://www.weizmann.ac.il/molgen/Sorek/ | title=Rotem Sorek's Lab Home Page }}

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.

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.{{cite journal |last1=Gallego del Sol |first1=Francisca |last2=Penadés |first2=José R. |last3=Marina |first3=Alberto |title=Deciphering the Molecular Mechanism Underpinning Phage Arbitrium Communication Systems |journal=Molecular Cell |date=April 2019 |volume=74 |issue=1 |pages=59–72.e3 |doi=10.1016/j.molcel.2019.01.025 |pmid=30745087 |pmc=6458997 }}{{cite journal |last1=Guan |first1=Zeyuan |last2=Pei |first2=Kai |last3=Wang |first3=Jing |last4=Cui |first4=Yongqing |last5=Zhu |first5=Xiang |last6=Su |first6=Xiang |last7=Zhou |first7=Yuanbao |last8=Zhang |first8=Delin |last9=Tang |first9=Chun |last10=Yin |first10=Ping |last11=Liu |first11=Zhu |last12=Zou |first12=Tingting |title=Structural insights into DNA recognition by AimR of the arbitrium communication system in the SPbeta phage |journal=Cell Discovery |date=28 May 2019 |volume=5 |issue=1 |page=29 |doi=10.1038/s41421-019-0101-2 |pmid=31149347 |pmc=6536502 }}{{cite journal |last1=Dou |first1=Chao |last2=Xiong |first2=Jie |last3=Gu |first3=Yijun |last4=Yin |first4=Kun |last5=Wang |first5=Jinjing |last6=Hu |first6=Yuehong |last7=Zhou |first7=Dan |last8=Fu |first8=Xianghui |last9=Qi |first9=Shiqian |last10=Zhu |first10=Xiaofeng |last11=Yao |first11=Shaohua |last12=Xu |first12=Heng |last13=Nie |first13=Chunlai |last14=Liang |first14=Zongan |last15=Yang |first15=Shengyong |last16=Wei |first16=Yuquan |last17=Cheng |first17=Wei |title=Structural and functional insights into the regulation of the lysis–lysogeny decision in viral communities |journal=Nature Microbiology |date=15 October 2018 |volume=3 |issue=11 |pages=1285–1294 |doi=10.1038/s41564-018-0259-7 |pmid=30323253 |s2cid=256703295 }} 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.

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.{{cite journal |last1=Stokar-Avihail |first1=Avigail |last2=Tal |first2=Nitzan |last3=Erez |first3=Zohar |last4=Lopatina |first4=Anna |last5=Sorek |first5=Rotem |title=Widespread Utilization of Peptide Communication in Phages Infecting Soil and Pathogenic Bacteria |journal=Cell Host & Microbe |date=May 2019 |volume=25 |issue=5 |pages=746–755.e5 |doi=10.1016/j.chom.2019.03.017 |pmid=31071296 |pmc=6986904 }} They speculate that "the occurrence of peptide-based communication systems among phages more broadly remains to be explored."

File:AimR bound to a DNA Operator in SPbeta Phages.png

The arbitrium system comprises 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.{{cite journal |last1=Maio |first1=Alessandro |last2=Brandi |first2=Letizia |last3=Donadio |first3=Stefano |last4=Gualerzi |first4=Claudio |title=The Oligopeptide Permease Opp Mediates Illicit Transport of the Bacterial P-site Decoding Inhibitor GE81112 |journal=Antibiotics |date=24 May 2016 |volume=5 |issue=2 |pages=17 |doi=10.3390/antibiotics5020017 |pmid=27231947 |pmc=4929432 |doi-access=free }} 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.{{cite journal |last1=Larsen |first1=Christopher N |last2=Sun |first2=Guangyu |last3=Li |first3=Xiaomei |last4=Zaremba |first4=Sam |last5=Zhao |first5=Hongtao |last6=He |first6=Sherry |last7=Zhou |first7=Liwei |last8=Kumar |first8=Sanjeev |last9=Desborough |first9=Vince |last10=Klem |first10=Edward B |title=Mat_peptide: comprehensive annotation of mature peptides from polyproteins in five virus families |journal=Bioinformatics |date=1 March 2020 |volume=36 |issue=5 |pages=1627–1628 |doi=10.1093/bioinformatics/btz777 |pmid=31609421 |pmc=8215913 }}{{cite journal |last1=Trinh |first1=Jimmy T. |last2=Zeng |first2=Lanying |title=Structure Regulates Phage Lysis–Lysogeny Decisions |journal=Trends in Microbiology |date=January 2019 |volume=27 |issue=1 |pages=3–4 |doi=10.1016/j.tim.2018.11.005 |pmid=30502931 |s2cid=54523229 }}

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.{{cite journal |last1=Brady |first1=Aisling |last2=Quiles-Puchalt |first2=Nuria |last3=Gallego del Sol |first3=Francisca |last4=Zamora-Caballero |first4=Sara |last5=Felipe-Ruíz |first5=Alonso |last6=Val-Calvo |first6=Jorge |last7=Meijer |first7=Wilfried J.J. |last8=Marina |first8=Alberto |last9=Penadés |first9=José R. |title=The arbitrium system controls prophage induction |journal=Current Biology |date=November 2021 |volume=31 |issue=22 |pages=5037–5045.e3 |doi=10.1016/j.cub.2021.08.072 |pmid=34562384 |pmc=8612738 |bibcode=2021CBio...31E5037B }}

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. Prof. Martha Clokie, of the University of Leicester, has hailed the discovery of viral communication as 'transformative'.

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• Quorum sensing - the corresponding phenomenon in bacteria

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Category:Phage proteins

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