Editing Bacteriophage (section)

== Replication ==
[[File:Phage injection.png|thumb|right|upright=2|Diagram of the DNA injection process]]
The life cycle of bacteriophages tends to be either a [[lytic cycle]] or a [[lysogenic cycle]]. In addition, some phages display pseudolysogenic behaviors.<ref name="Popescu">{{cite journal | vauthors = Popescu M, Van Belleghem JD, Khosravi A, Bollyky PL | title = Bacteriophages and the Immune System | journal = Annual Review of Virology | volume = 8 | issue = 1 | pages = 415–435 | date = September 2021 | pmid = 34014761 | doi = 10.1146/annurev-virology-091919-074551 | doi-access = free }}</ref>

With ''lytic phages'' such as the [[T4 phage]], bacterial cells are broken open (lysed) and destroyed after immediate replication of the virion. As soon as the cell is destroyed, the phage progeny can find new hosts to infect.<ref name="Popescu"/> Lytic phages are more suitable for [[phage therapy]]. Some lytic phages undergo a phenomenon known as lysis inhibition, where completed phage progeny will not immediately lyse out of the cell if extracellular phage concentrations are high. This mechanism is not identical to that of the [[Temperateness (virology)|temperate phage]] going dormant and usually is temporary.<ref>{{cite journal | vauthors = Abedon ST | title = Look Who's Talking: T-Even Phage Lysis Inhibition, the Granddaddy of Virus-Virus Intercellular Communication Research | journal = Viruses | volume = 11 | issue = 10 | page = 951 | date = October 2019 | pmid = 31623057 | pmc = 6832632 | doi = 10.3390/v11100951 | doi-access = free }}</ref>

In contrast, the ''[[lysogenic cycle]]'' does not result in immediate lysing of the host cell. Those phages able to undergo lysogeny are known as [[temperate phage]]s. Their viral genome will integrate with host DNA and replicate along with it, relatively harmlessly, or may even become established as a [[plasmid]]. The virus remains dormant until host conditions deteriorate, perhaps due to depletion of nutrients, then, the [[endogenous]] phages (known as [[prophage]]s) become active. At this point they initiate the reproductive cycle, resulting in lysis of the host cell. As the lysogenic cycle allows the host cell to continue to survive and reproduce, the virus is replicated in all offspring of the cell. An example of a bacteriophage known to follow the lysogenic cycle and the lytic cycle is the [[phage lambda]] of ''E. coli.''<ref>{{cite book | vauthors = Mason KA, Losos JB, Singer SR, Raven PH, Johnson GB | date = 2011 | title = Biology | page = 533 | publisher = McGraw-Hill | location = New York | isbn = 978-0-07-893649-4 }}</ref>

Sometimes prophages may provide benefits to the host bacterium while they are dormant by adding new functions to the bacterial [[genome]], in a phenomenon called [[lysogenic conversion]]. Examples are the conversion of harmless strains of ''[[Corynebacterium diphtheriae]]'' or ''[[Vibrio cholerae]]'' by bacteriophages to highly virulent ones that cause [[diphtheria]] or [[cholera]], respectively.<ref name="pmid19007916">{{cite journal | vauthors = Mokrousov I | title = Corynebacterium diphtheriae: genome diversity, population structure and genotyping perspectives | journal = Infection, Genetics and Evolution | volume = 9 | issue = 1 | pages = 1–15 | date = January 2009 | pmid = 19007916 | doi = 10.1016/j.meegid.2008.09.011 | bibcode = 2009InfGE...9....1M }}</ref><ref name="pmid21799407">{{cite journal | vauthors = Charles RC, Ryan ET | title = Cholera in the 21st century | journal = Current Opinion in Infectious Diseases | volume = 24 | issue = 5 | pages = 472–477 | date = October 2011 | pmid = 21799407 | doi = 10.1097/QCO.0b013e32834a88af | s2cid = 6907842 }}</ref> Strategies to combat certain bacterial infections by targeting these toxin-encoding prophages have been proposed.<ref>{{cite journal | vauthors = Keen EC | title = Paradigms of pathogenesis: targeting the mobile genetic elements of disease | journal = Frontiers in Cellular and Infection Microbiology | volume = 2 | page = 161 | date = December 2012 | pmid = 23248780 | pmc = 3522046 | doi = 10.3389/fcimb.2012.00161 | doi-access = free }}</ref>

=== Attachment and penetration ===

[[File:Phage.jpg|thumb|In this [[electron micrograph]] of bacteriophages attached to a bacterial cell, the viruses are the size and shape of coliphage T1 ]]
<!-- Deleted image removed: [[File:Trialphage.jpg|thumb|A 3D rendering of a T4 type bacteriophage landing on a bacterium to inject genetic material]] -->
Bacterial cells are protected by a cell wall of [[polysaccharide]]s, which are important virulence factors protecting bacterial cells against both immune host defenses and [[antibiotic]]s.<ref>{{cite journal | vauthors = Drulis-Kawa Z, Majkowska-Skrobek G, Maciejewska B | title = Bacteriophages and phage-derived proteins--application approaches | journal = Current Medicinal Chemistry | volume = 22 | issue = 14 | pages = 1757–1773 | year = 2015 | pmid = 25666799 | pmc = 4468916 | doi = 10.2174/0929867322666150209152851 }}</ref> {{citation needed span|date=November 2021|To enter a host cell, bacteriophages bind to specific receptors on the surface of bacteria, including [[lipopolysaccharide]]s, [[teichoic acid]]s, [[protein]]s, or even [[flagella]]. This specificity means a bacteriophage can infect only certain bacteria bearing receptors to which they can bind, which in turn, determines the phage's host range. Polysaccharide-degrading enzymes are virion-associated proteins that enzymatically degrade the capsular outer layer of their hosts at the initial step of a tightly programmed phage infection process.}}
Host growth conditions also influence the ability of the phage to attach and invade them.<ref name="pmid9356254">{{cite journal | vauthors = Gabashvili IS, Khan SA, Hayes SJ, Serwer P | title = Polymorphism of bacteriophage T7 | journal = Journal of Molecular Biology | volume = 273 | issue = 3 | pages = 658–667 | date = October 1997 | pmid = 9356254 | doi = 10.1006/jmbi.1997.1353 }}</ref> As phage virions do not move independently, they must rely on random encounters with the correct receptors when in solution, such as blood, lymphatic circulation, irrigation, soil water, etc.{{citation needed|date=October 2022}}

Myovirus bacteriophages use a [[hypodermic syringe]]-like motion to inject their genetic material into the cell. After contacting the appropriate receptor, the tail fibers flex to bring the base plate closer to the surface of the cell. This is known as reversible binding. Once attached completely, irreversible binding is initiated and the tail contracts, possibly with the help of [[Adenosine triphosphate|ATP]] present in the tail,<ref name="Prescott" /> injecting genetic material through the bacterial membrane.<ref name="Maghsoodi Chatterjee Andricioaei Perkins pp. 25097–25105">{{cite journal | vauthors = Maghsoodi A, Chatterjee A, Andricioaei I, Perkins NC | title = How the phage T4 injection machinery works including energetics, forces, and dynamic pathway | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 116 | issue = 50 | pages = 25097–25105 | date = December 2019 | pmid = 31767752 | pmc = 6911207 | doi = 10.1073/pnas.1909298116 | doi-access = free | bibcode = 2019PNAS..11625097M }}</ref> The injection is accomplished through a sort of bending motion in the shaft by going to the side, contracting closer to the cell and pushing back up. Podoviruses lack an elongated tail sheath like that of a myovirus, so instead, they use their small, tooth-like tail fibers enzymatically to degrade a portion of the cell membrane before inserting their genetic material.

=== Synthesis of proteins and nucleic acid ===
Within minutes, bacterial [[ribosome]]s start translating viral mRNA into protein. For RNA-based phages, [[RNA replicase]] is synthesized early in the process. Proteins modify the bacterial [[RNA polymerase]] so it preferentially transcribes viral mRNA. The host's normal synthesis of proteins and nucleic acids is disrupted, and it is forced to manufacture viral products instead. These products go on to become part of new virions within the cell, helper proteins that contribute to the assemblage of new virions, or proteins involved in cell [[lysis]]. In 1972, [[Walter Fiers]] ([[University of Ghent]], [[Belgium]]) was the first to establish the complete nucleotide sequence of a gene and in 1976, of the viral genome of [[bacteriophage MS2]].<ref>{{cite journal | vauthors = Fiers W, Contreras R, Duerinck F, Haegeman G, Iserentant D, Merregaert J, Min Jou W, Molemans F, Raeymaekers A, Van den Berghe A, Volckaert G, Ysebaert M | title = Complete nucleotide sequence of bacteriophage MS2 RNA: primary and secondary structure of the replicase gene | journal = Nature | volume = 260 | issue = 5551 | pages = 500–507 | date = April 1976 | pmid = 1264203 | doi = 10.1038/260500a0 | s2cid = 4289674 | bibcode = 1976Natur.260..500F }}</ref> Some [[DNA#ssDNA vs. dsDNA|dsDNA]] bacteriophages encode ribosomal proteins, which are thought to modulate protein translation during phage infection.<ref>{{cite journal | vauthors = Mizuno CM, Guyomar C, Roux S, Lavigne R, Rodriguez-Valera F, Sullivan MB, Gillet R, Forterre P, Krupovic M | title = Numerous cultivated and uncultivated viruses encode ribosomal proteins | journal = Nature Communications | volume = 10 | issue = 1 | page = 752 | date = February 2019 | pmid = 30765709 | pmc = 6375957 | doi = 10.1038/s41467-019-08672-6 | bibcode = 2019NatCo..10..752M }}</ref>

=== Virion assembly ===
In the case of the [[T4 phage]], the construction of new virus particles involves the assistance of helper proteins that act catalytically during phage [[morphogenesis]].<ref name="pmid4878023">{{cite journal | vauthors = Snustad DP | title = Dominance interactions in Escherichia coli cells mixedly infected with bacteriophage T4D wild-type and amber mutants and their possible implications as to type of gene-product function: catalytic vs. stoichiometric | journal = Virology | volume = 35 | issue = 4 | pages = 550–563 | date = August 1968 | pmid = 4878023 | doi = 10.1016/0042-6822(68)90285-7 }}</ref> The base plates are assembled first, with the tails being built upon them afterward. The head capsids, constructed separately, will spontaneously assemble with the tails. During assembly of the [[Escherichia virus T4|phage T4]] [[virus|virion]], the morphogenetic proteins encoded by the phage [[gene]]s interact with each other in a characteristic sequence. Maintaining an appropriate balance in the amounts of each of these proteins produced during viral infection appears to be critical for normal phage T4 [[morphogenesis]].<ref name="pmid4907266">{{cite journal | vauthors = Floor E | title = Interaction of morphogenetic genes of bacteriophage T4 | journal = Journal of Molecular Biology | volume = 47 | issue = 3 | pages = 293–306 | date = February 1970 | pmid = 4907266 | doi = 10.1016/0022-2836(70)90303-7 }}</ref> The DNA is packed efficiently within the heads.<ref>{{cite journal | vauthors = Petrov AS, Harvey SC | title = Packaging double-helical DNA into viral capsids: structures, forces, and energetics | journal = Biophysical Journal | volume = 95 | issue = 2 | pages = 497–502 | date = July 2008 | pmid = 18487310 | pmc = 2440449 | doi = 10.1529/biophysj.108.131797 | bibcode = 2008BpJ....95..497P }}</ref> The whole process takes about 15 minutes.

Early studies of bactioriophage T4 (1962–1964) provided an opportunity to gain understanding of  virtually all of the genes that are essential for growth of the bacteriophage under laboratory conditions.<ref>Edgar RS Conditional lethals: in Phage and the Origins of Molecular Biology (2007) Edited by John Cairns, Gunther S. Stent, and James D. Watson, Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, Long Island, New York {{ISBN|978-0-87969-800-3}}</ref><ref name="pmid15514035">{{cite journal | vauthors = Edgar B | title = The genome of bacteriophage T4: an archeological dig | journal = Genetics | volume = 168 | issue = 2 | pages = 575–82 | date = October 2004 | doi = 10.1093/genetics/168.2.575 | pmid = 15514035 | pmc = 1448817 }}</ref>  These studies were made possible by the availability of two classes of [[lethal allele|conditional lethal mutants]].<ref name="EpsteinBolle1963">{{cite journal|vauthors = Epstein RH, Bolle A, Steinberg CM, Kellenberger E, Boy de la Tour E, Chevalley R, Edgar RS, Susman M, Denhardt GH, Lielausis A|title = Physiological Studies of Conditional Lethal Mutants of Bacteriophage T4D|journal = Cold Spring Harbor Symposia on Quantitative Biology|volume = 28|year = 1963|pages = 375–394|issn = 0091-7451|doi = 10.1101/SQB.1963.028.01.053}}</ref> One class of such mutants was referred to as [[stop codon|amber mutants]].<ref name="EpsteinBolle1963"/>  The other class of conditional lethal mutants was referred to as [[temperature-sensitive mutant]]s<ref name="pmid14156925">{{cite journal | vauthors = Edgar RS, Lielausis I | title = Temperature-sensitive mutants of bacteriophage T4D: Their isolation and Characterization.| journal = Genetics | volume = 49 | pages = 649–62 | date = April 1964 | issue = 4| doi = 10.1093/genetics/49.4.649| pmid = 14156925 | pmc = 1210603}}</ref>  Studies of these two classes of mutants led to considerable insight into  the functions and interactions of the proteins employed in the machinery of [[DNA replication]], [[DNA repair|repair]] and [[genetic recombination|recombination]], and on how viruses are assembled from protein and nucleic acid components (molecular [[morphogenesis]]).

=== Release of virions ===
Phages may be released via cell lysis, by extrusion, or, in a few cases, by budding. Lysis, by tailed phages, is achieved by an enzyme called [[endolysin]], which attacks and breaks down the cell wall [[peptidoglycan]]. An altogether different phage type, the [[filamentous phage]], makes the host cell continually secrete new virus particles. Released virions are described as free, and, unless defective, are capable of infecting a new bacterium. Budding is associated with certain ''[[Mycoplasma]]'' phages. In contrast to virion release, phages displaying a [[lysogenic]] cycle do not kill the host and instead become long-term residents as [[prophage]]s.<ref name="pmid36164818">{{cite journal | vauthors = Henrot C, Petit MA | title = Signals triggering prophage induction in the gut microbiota | journal = Molecular Microbiology | volume = 118 | issue = 5 | pages = 494–502 | date = November 2022 | pmid = 36164818 | pmc = 9827884 | doi = 10.1111/mmi.14983 | s2cid = 252542284 }}</ref>

=== Communication ===
Research in 2017 revealed that the bacteriophage Φ3T makes a short viral protein that signals other bacteriophages to lie dormant instead of killing the host bacterium. [[Arbitrium]] is the name given to this protein by the researchers who discovered it.<ref name = EwenCallaway2017>{{cite journal | vauthors = Callaway E | doi = 10.1038/nature.2017.21313 | doi-access= free | url = https://www.nature.com/news/do-you-speak-virus-phages-caught-sending-chemical-messages-1.21313 | title = Do you speak virus? Phages caught sending chemical messages | journal = Nature | year = 2017 }}</ref><ref name="Erez2017">{{cite journal | vauthors = Erez Z, Steinberger-Levy I, Shamir M, Doron S, Stokar-Avihail A, Peleg Y, Melamed S, Leavitt A, Savidor A, Albeck S, Amitai G, Sorek R | title = Communication between viruses guides lysis-lysogeny decisions | journal = Nature | volume = 541 | issue = 7638 | pages = 488–493 | date = January 2017 | pmid = 28099413 | pmc = 5378303 | doi = 10.1038/nature21049 | bibcode = 2017Natur.541..488E }}</ref>