Bacteriophage

A bacteriophage (/bækˈtɪərioʊfeɪdʒ/), also known informally as

a phage (/ˈfeɪdʒ/), is a virus that infects and replicates within
bacteria and archaea. The term was derived from "bacteria" and
the Greek φαγεῖν (phagein), 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 (e.g.
MS2) and as many as hundreds of genes. Phages replicate within
the bacterium following the injection of their genome into its
cytoplasm.

Bacteriophages are among the most common and diverse entities

in the biosphere.[2] Bacteriophages are ubiquitous viruses, found Structural model at atomic resolution
wherever bacteria exist. It is estimated there are more than 1031 of bacteriophage T4[1]
bacteriophages on the planet, more than every other organism on
Earth, including bacteria, combined.[3] Viruses are the most
abundant biological entity in the water column of the world's
oceans, and the second largest component of biomass after
prokaryotes,[4] where up to 9x108 virions per millilitre have been
found in microbial mats at the surface,[5] and up to 70% of marine
bacteria may be infected by phages.[6]

Phages have been used since the late 20th century as an alternative
to antibiotics in the former Soviet Union and Central Europe, as
well as in France.[7][8] They are seen as a possible therapy against
multi-drug-resistant strains of many bacteria (see phage therapy).[9]
On the other hand, phages of Inoviridae have been shown to
complicate biofilms involved in pneumonia and cystic fibrosis and
to shelter the bacteria from drugs meant to eradicate disease, thus
promoting persistent infection.[10]
The structure of a typical myovirus
bacteriophage

Contents
Classification
History
Nobel prizes awarded for phage research
Uses
Phage therapy
Other
Detriments Anatomy and infection cycle of
Dairy industry phage T4.
Replication
 Attachment and penetration
Synthesis of proteins and nucleic acid
Virion assembly
Release of virions
Communication
Genome structure
Systems biology
In the environment
In humans
Commonly studied bacteriophage
See also
References
Bibliography
External links

Classification
Bacteriophages occur abundantly in the biosphere, with different genomes, and lifestyles. Phages are
classified by the International Committee on Taxonomy of Viruses (ICTV) according to morphology and
nucleic acid.

Bacteriophage P22, a member of the

Podoviridae by morphology due to its
short, non-contractile tail
 ICTV classification of prokaryotic (bacterial and archaeal) viruses[2]
Order Family Morphology Nucleic acid Examples
Enveloped,
Belfryvirales Turriviridae Linear dsDNA
isometric
Nonenveloped,
Ackermannviridae Linear dsDNA
contractile tail
Nonenveloped,
Autographiviridae noncontractile tail Linear dsDNA
(short)
Chaseviridae Linear dsDNA
Demerecviridae Linear dsDNA
Drexlerviridae Linear dsDNA
Guenliviridae Linear dsDNA
Nonenveloped,
Herelleviridae Linear dsDNA
contractile tail
Caudovirales Nonenveloped,
Myoviridae Linear dsDNA T4, Mu, P1, P2
contractile tail
Nonenveloped,
Siphoviridae noncontractile tail Linear dsDNA λ, T5, HK97, N15
(long)
Nonenveloped,
Podoviridae noncontractile tail Linear dsDNA T7, T3, Φ29, P22
(short)
Rountreeviridae Linear dsDNA
Salasmaviridae Linear dsDNA
Schitoviridae Linear dsDNA
Zobellviridae Linear dsDNA
Enveloped,
Sphaerolipoviridae Linear dsDNA
isometric
Enveloped,
Halopanivirales Simuloviridae Linear dsDNA
isometric
Enveloped,
Matshushitaviridae Linear dsDNA
isometric
Enveloped, Circular ssDNA, circular
Haloruvirales Pleolipoviridae
pleomorphic dsDNA, or linear dsDNA
Nonenveloped,
Kalamavirales Tectiviridae Linear dsDNA
isometric
Enveloped, rod- Acidianus
Lipothrixviridae Linear dsDNA
shaped filamentous virus 1
Ligamenvirales
Nonenveloped, rod- Sulfolobus islandicus
Rudiviridae Linear dsDNA
shaped rod-shaped virus 1
Mindivirales Cystoviridae Enveloped, spherical Linear dsRNA Φ6
Norzivirales Nonenveloped,
Atkinsviridae Linear ssRNA
isometric
Nonenveloped,
Duinviridae Linear ssRNA
isometric
 Fiersviridae Nonenveloped, Linear ssRNA MS2, Qβ
isometric
Nonenveloped,
Solspiviridae Linear ssRNA
isometric
Nonenveloped,
Petitvirales Microviridae Circular ssDNA ΦX174
isometric
Enveloped, rod-
Primavirales Tristromaviridae Linear dsDNA
shaped
Nonenveloped,
Blumeviridae Linear ssRNA
isometric
Timlovirales
Nonenveloped,
Steitzviridae Linear ssRNA
isometric
Nonenveloped,
Inoviridae Circular ssDNA M13
filamentous
Nonenveloped,
Tubulavirales Paulinoviridae Circular ssDNA
filamentous
Nonenveloped,
Plectroviridae Circular ssDNA
filamentous
Nonenveloped,
Vinavirales Corticoviridae Circular dsDNA PM2
isometric
Picobirnaviridae Nonenveloped,
Durnavirales Linear dsRNA
(proposal) isometric
Enveloped, bottle-
Ampullaviridae Linear dsDNA
shaped
Nonenveloped,
Autolykiviridae Linear dsDNA
isometric
Nonenveloped,
Bicaudaviridae Circular dsDNA
lemon-shaped
Nonenveloped, rod-
Clavaviridae Circular dsDNA
shaped
Nonenveloped,
Finnlakeviridae Circular ssDNA FLiP[11]
isometric
Nonenveloped,
Fuselloviridae Circular dsDNA
lemon-shaped
Unassigned Enveloped,
Globuloviridae Linear dsDNA
isometric
Guttaviridae Nonenveloped, ovoid Circular dsDNA
Nonenveloped,
Halspiviridae Linear dsDNA
lemon-shaped
Enveloped,
Plasmaviridae Circular dsDNA
pleomorphic
Enveloped,
Portogloboviridae Circular dsDNA
isometric
Nonenveloped,
Thaspiviridae Linear dsDNA
lemon-shaped
Nonnveloped, rod-
Spiraviridae Circular ssDNA
shaped

It has been suggested that members of Picobirnaviridae infect bacteria, but not mammals.[12]
There are also many unassigned genera of the class Leviviricetes: Chimpavirus, Hohglivirus, Mahrahvirus,
Meihzavirus, Nicedsevirus, Sculuvirus, Skrubnovirus, Tetipavirus and Winunavirus containing linear
ssRNA genomes[13] and the unassigned genus Lilyvirus of the order Caudovirales containing a linear
dsDNA genome.

History
In 1896, Ernest Hanbury Hankin reported that something in the waters of
the Ganges and Yamuna rivers in India had a marked antibacterial action
against cholera and it could pass through a very fine porcelain filter.[14] In
1915, British bacteriologist Frederick Twort, superintendent of the Brown
Institution of London, discovered a small agent that infected and killed
bacteria. He believed the agent must be one of the following:

1. a stage in the life cycle of the bacteria

2. an enzyme produced by the bacteria themselves, or
3. a virus that grew on and destroyed the bacteria[15]

Twort's research was interrupted by the onset of World War I, as well as a

shortage of funding and the discoveries of antibiotics. Félix d'Herelle

Independently, French-Canadian microbiologist Félix d'Hérelle, working

at the Pasteur Institute in Paris, announced on 3 September 1917, that he had discovered "an invisible,
antagonistic microbe of the dysentery bacillus". For d’Hérelle, there was no question as to the nature of his
discovery: "In a flash I had understood: what caused my clear spots was in fact an invisible microbe… a
virus parasitic on bacteria."[16] D'Hérelle called the virus a bacteriophage, a bacteria-eater (from the Greek
phagein meaning "to devour"). He also recorded a dramatic account of a man suffering from dysentery
who was restored to good health by the bacteriophages.[17] It was D'Herelle who conducted much research
into bacteriophages and introduced the concept of phage therapy.[18]

Nobel prizes awarded for phage research

In 1969, Max Delbrück, Alfred Hershey, and Salvador Luria were awarded the Nobel Prize in Physiology
or Medicine for their discoveries of the replication of viruses and their genetic structure.[19] Specifically the
work of Hershey, as contributor to the Hershey–Chase experiment in 1952 provided convincing evidence
that DNA, not protein, was the genetic material of life. Delbrück and Luria carried out the Luria–Delbrück
experiment which demonstrated statistically that mutations in bacteria occur randomly and thus follow
Darwinian rather than Lamarckian principles.

Uses

Phage therapy

Phages were discovered to be antibacterial agents and were used in the former Soviet Republic of Georgia
(pioneered there by Giorgi Eliava with help from the co-discoverer of bacteriophages, Félix d'Herelle)
during the 1920s and 1930s for treating bacterial infections. They had widespread use, including treatment
of soldiers in the Red Army. However, they were abandoned for general use in the West for several
reasons:
 Antibiotics were discovered and marketed widely. They were easier to make, store, and to
prescribe.
Medical trials of phages were carried out, but a basic lack of understanding raised questions
about the validity of these trials.[20]
Publication of research in the Soviet Union was mainly in the Russian or Georgian
languages and for many years, was not followed internationally.

The use of phages has continued since the end of the Cold War in Russia,[21] Georgia and elsewhere in
Central and Eastern Europe. The first regulated, randomized, double-blind clinical trial was reported in the
Journal of Wound Care in June 2009, which evaluated the safety and efficacy of a bacteriophage cocktail
to treat infected venous ulcers of the leg in human patients.[22] The FDA approved the study as a Phase I
clinical trial. The study's results demonstrated the safety of therapeutic application of bacteriophages, but
did not show efficacy. The authors explained that the use of certain chemicals that are part of standard
wound care (e.g. lactoferrin or silver) may have interfered with bacteriophage viability.[22] Shortly after
that, another controlled clinical trial in Western Europe (treatment of ear infections caused by Pseudomonas
aeruginosa) was reported in the journal Clinical Otolaryngology in August 2009.[23] The study concludes
that bacteriophage preparations were safe and effective for treatment of chronic ear infections in humans.
Additionally, there have been numerous animal and other experimental clinical trials evaluating the efficacy
of bacteriophages for various diseases, such as infected burns and wounds, and cystic fibrosis associated
lung infections, among others.[23]

Meanwhile, bacteriophage researchers have been developing engineered viruses to overcome antibiotic
resistance, and engineering the phage genes responsible for coding enzymes that degrade the biofilm
matrix, phage structural proteins, and the enzymes responsible for lysis of the bacterial cell wall.[5][6][7]
There have been results showing that T4 phages that are small in size and short-tailed, can be helpful in
detecting E. coli in the human body.[24]

Therapeutic efficacy of a phage cocktail was evaluated in a mice model with nasal infection of multidrug-
resistant (MDR) A. baumannii. Mice treated with the phage cocktail showed a 2.3-fold higher survival rate
than those untreated in seven days post infection.[25] In 2017 a patient with a pancreas compromised by
MDR A. baumannii was put on several antibiotics, despite this the patient's health continued to deteriorate
during a four-month period. Without effective antibiotics the patient was subjected to phage therapy using a
phage cocktail containing nine different phages that had been demonstrated to be effective against MDR A.
baumannii. Once on this therapy the patient's downward clinical trajectory reversed, and returned to
health.[26]

D'Herelle "quickly learned that bacteriophages are found wherever bacteria thrive: in sewers, in rivers that
catch waste runoff from pipes, and in the stools of convalescent patients."[27] This includes rivers
traditionally thought to have healing powers, including India's Ganges River.[28]

Other

Food industry – Phages have increasingly been used to safen food products, and to forestall spoilage
bacteria.[29] Since 2006, the United States Food and Drug Administration (FDA) and United States
Department of Agriculture (USDA) have approved several bacteriophage products. LMP-102 (Intralytix)
was approved for treating ready-to-eat (RTE) poultry and meat products. In that same year, the FDA
approved LISTEX (developed and produced by Micreos) using bacteriophages on cheese to kill Listeria
monocytogenes bacteria, in order to give them generally recognized as safe (GRAS) status.[30] In July
2007, the same bacteriophage were approved for use on all food products.[31] In 2011 USDA confirmed
that LISTEX is a clean label processing aid and is included in USDA.[32] Research in the field of food
safety is continuing to see if lytic phages are a viable option to control other food-borne pathogens in
various food products.

Diagnostics – In 2011, the FDA cleared the first bacteriophage-based product for in vitro diagnostic
use.[33] The KeyPath MRSA/MSSA Blood Culture Test uses a cocktail of bacteriophage to detect
Staphylococcus aureus in positive blood cultures and determine methicillin resistance or susceptibility. The
test returns results in about five hours, compared to two to three days for standard microbial identification
and susceptibility test methods. It was the first accelerated antibiotic-susceptibility test approved by the
FDA.[34]

Counteracting bioweapons and toxins – Government agencies in the West have for several years been
looking to Georgia and the former Soviet Union for help with exploiting phages for counteracting
bioweapons and toxins, such as anthrax and botulism.[35] Developments are continuing among research
groups in the U.S. Other uses include spray application in horticulture for protecting plants and vegetable
produce from decay and the spread of bacterial disease. Other applications for bacteriophages are as
biocides for environmental surfaces, e.g., in hospitals, and as preventative treatments for catheters and
medical devices before use in clinical settings. The technology for phages to be applied to dry surfaces,
e.g., uniforms, curtains, or even sutures for surgery now exists. Clinical trials reported in Clinical
Otolaryngology[23] show success in veterinary treatment of pet dogs with otitis.

The SEPTIC bacterium sensing and identification method uses the ion emission and its dynamics during
phage infection and offers high specificity and speed for detection.[36]

Phage display is a different use of phages involving a library of phages with a variable peptide linked to a
surface protein. Each phage genome encodes the variant of the protein displayed on its surface (hence the
name), providing a link between the peptide variant and its encoding gene. Variant phages from the library
may be selected through their binding affinity to an immobilized molecule (e.g., botulism toxin) to
neutralize it. The bound, selected phages can be multiplied by reinfecting a susceptible bacterial strain, thus
allowing them to retrieve the peptides encoded in them for further study.[37]

Antimicrobial drug discovery – Phage proteins often have antimicrobial activity and may serve as leads
for peptidomimetics, i.e. drugs that mimic peptides.[38] Phage-ligand technology makes use of phage
proteins for various applications, such as binding of bacteria and bacterial components (e.g. endotoxin) and
lysis of bacteria.[39]

Basic research – Bacteriophages are important model organisms for studying principles of evolution and
ecology.[40]

Detriments

Dairy industry

Bacteriophages present in the environment can cause cheese to not ferment. In order to avoid this, mixed-
strain starter cultures and culture rotation regimes can be used.[41] Genetic engineering of culture microbes -
especially Lactococcus lactis and Streptococcus thermophilus - have been studied for genetic analysis and
modification to improve phage resistance. This has especially focused on plasmid and recombinant
chromosomal modifications.[42][29]

Replication
Bacteriophages may have a
lytic cycle or a lysogenic cycle.
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. 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 Diagram of the DNA injection process
concentrations are high. This
mechanism is not identical to
that of temperate phage going dormant and usually, is temporary.

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 phages. 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 prophages) 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.[43]

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.[44][45] Strategies to combat certain
bacterial infections by targeting these toxin-encoding prophages have been proposed.[46]

Attachment and penetration

Bacterial cells are protected by a cell wall of polysaccharides, which are important virulence factors
protecting bacterial cells against both immune host defenses and antibiotics.[47] To enter a host cell,
bacteriophages bind to specific receptors on the surface of bacteria, including lipopolysaccharides, teichoic
acids, proteins, 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.[48] 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.

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 ATP present in the
tail,[6] injecting genetic material through the bacterial
membrane.[49] 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 ribosomes start translating viral mRNA

into protein. For RNA-based phages, RNA replicase is
synthesized early in the process. Proteins modify the bacterial In this electron micrograph of
RNA polymerase so it preferentially transcribes viral mRNA. The bacteriophages attached to a
host's normal synthesis of proteins and nucleic acids is disrupted, bacterial cell, the viruses are the
and it is forced to manufacture viral products instead. These size and shape of coliphage T1
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.[50] Some dsDNA bacteriophages encode ribosomal proteins, which are thought to modulate protein
translation during phage infection.[51]

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.[52] 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 phage T4 virion, the morphogenetic proteins encoded by
the phage genes 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.[53] The DNA is packed efficiently within the heads.[54] The whole process takes about
15 minutes.

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, make 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 but, rather, become long-term residents as prophage.

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.[55][56]
 Genome structure
Given the millions of different phages in the environment, phage genomes come in a variety of forms and
sizes. RNA phage such as MS2 have the smallest genomes, of only a few kilobases. However, some DNA
phage such as T4 may have large genomes with hundreds of genes; the size and shape of the capsid varies
along with the size of the genome.[57] The largest bacteriophage genomes reach a size of 735 kb.[58]

the 44 kb T7 phage genome. Each box is a gene. Numbers indicate genes (or rather open reading frames).[59]

Bacteriophage genomes can be highly mosaic, i.e. the genome of many phage species appear to be
composed of numerous individual modules. These modules may be found in other phage species in
different arrangements. Mycobacteriophages, bacteriophages with mycobacterial hosts, have provided
excellent examples of this mosaicism. In these mycobacteriophages, genetic assortment may be the result of
repeated instances of site-specific recombination and illegitimate recombination (the result of phage genome
acquisition of bacterial host genetic sequences).[60] Evolutionary mechanisms shaping the genomes of
bacterial viruses vary between different families and depend upon the type of the nucleic acid,
characteristics of the virion structure, as well as the mode of the viral life cycle.[61]

Some marine roseobacter phage contain deoxyuridine (dU) instead of deoxythymidine (dT) in their
genomic DNA. There is some evidence that this unusual component is a mechanism to evade bacterial
defense mechanisms such as restriction endonucleases and CRISPR/Cas systems which evolved to
recognize and cleave sequences within invading phage, thereby inactivating them. Other phages have long
been known to use unusual nucleotides. In 1963, Takahashi and Marmur identified a Bacillus phage that
has dU substituting dT in its genome,[62] and in 1977, Kirnos et al. identified a cyanophage containing 2-
aminoadenine (Z) instead of adenine (A).[63]

Systems biology
The field of systems biology investigates the complex networks of interactions within an organism, usually
using computational tools and modeling.[64] For example, a phage genome that enters into a bacterial host
cell may express hundreds of phage proteins which will affect the expression of numerous host gene or the
host's metabolism. All of these complex interactions can be described and simulated in computer
models.[64]

For instance, infection of Pseudomonas aeruginosa by the temperate phage PaP3 changed the expression
of 38% (2160/5633) of its host's genes. Many of these effects are probably indirect, hence the challenge
becomes to identify the direct interactions among bacteria and phage.[65]

Several attempts have been made to map protein–protein interactions among phage and their host. For
instance, bacteriophage lambda was found to interact with its host, E. coli, by dozens of interactions.
Again, the significance of many of these interactions remains unclear, but these studies suggest that there
most likely are several key interactions and many indirect interactions whose role remains
uncharacterized.[66]
In the environment
Metagenomics has allowed the in-water detection of bacteriophages that was not possible previously.[67]

Also, bacteriophages have been used in hydrological tracing and modelling in river systems, especially
where surface water and groundwater interactions occur. The use of phages is preferred to the more
conventional dye marker because they are significantly less absorbed when passing through ground waters
and they are readily detected at very low concentrations.[68] Non-polluted water may contain
approximately 2×108 bacteriophages per ml.[69]

Bacteriophages are thought to contribute extensively to horizontal gene transfer in natural environments,
principally via transduction, but also via transformation.[70] Metagenomics-based studies also have revealed
that viromes from a variety of environments harbor antibiotic-resistance genes, including those that could
confer multidrug resistance.[71]

In humans
Although phage do not infect humans, there are countless phage particles in the human body, given our
extensive microbiome. Our phage population has been called the human phageome, including the "healthy
gut phageome" (HGP) and the "diseased human phageome" (DHP).[72] The active phageome of a healthy
human (i.e., actively replicating as opposed to nonreplicating, integrated prophage) has been estimated to
comprise dozens to thousands of different viruses.[73] There is evidence that bacteriophage and bacteria
interact in the human gut microbiome both antagonistically and beneficially.[74]

Preliminary studies have indicated that common bacteriophage are found on average in 62% of healthy
individuals, while their prevalence was reduced by 42% and 54% on average in patients with ulcerative
colitis (UC) and Crohn’s disease (CD).[72] Abundance of phages may also decline in the elderly.[74]

The most common phages in the human intestine, found worldwide, are crAssphage. CrAssphages are
transmitted from mother to child soon after birth, and there is some evidence suggesting that they may
transmitted locally. Each person develops their own unique crAss-phage clusters. CrAss-like phages also
may be present in primates besides humans.[74]

Commonly studied bacteriophage

Among the countless phage, only a few have been studied in detail, including some historically important
phage that were discovered in the early days of microbial genetics. These, especially the T-phage, helped to
discover important principles of gene structure and function.

186 phage
λ phage
Φ6 phage
Φ29 phage
ΦX174
Bacteriophage φCb5
G4 phage
M13 phage
MS2 phage (23–28 nm in size)[75]
N4 phage
 P1 phage
P2 phage
P4 phage
R17 phage
T2 phage
T4 phage (169 kbp genome,[76] 200 nm long[77])
T7 phage
T12 phage

See also
Bacterivore
CrAssphage
CRISPR
DNA viruses
Phage ecology
Phage monographs (a comprehensive listing of phage and phage-associated monographs,
1921–present)
Phagemid
Polyphage
RNA viruses
Transduction
Viriome
Virophage, viruses that infect other viruses

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External links
Häusler T (2006). Viruses vs. superbugs : a solution to the antibiotics crisis?. London:
Macmillan. ISBN 978-1-4039-8764-8.
Abedon ST. "The Bacteriophage Ecology Group" (https://web.archive.org/web/20130603163
753/http://www.phage.org/). The Ohio State University. Archived from the original (http://ww
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Tourterel C, Blouin Y. "Bacteriophages illustrations and genomics" (http://bacteriophages.ig
mors.u-psud.fr/). Orsay phage web site.
 "QuipStories: Bacteriophages get a foothold on their prey" (http://www.ebi.ac.uk/pdbe/widget
s/QuipStories/T4tail/T4tail.pdf) (PDF). PDBe.
Flatow I (April 2008). "Using 'Phage' Viruses to Help Fight Infection" (https://web.archive.org/
web/20080417232145/http://www.sciencefriday.com/program/archives/200804043). Science
Friday podcast. NPR. Archived from the original (http://www.sciencefriday.com/program/arch
ives/200804043) on 17 April 2008.
"Animation of a scientifically correct T4 bacteriophage targeting E. coli bacteria" (https://ww
w.youtube.com/watch?v=V73nEGXUeBY). YouTube.
"T4 Bacteriophage targeting E. coli bacteria" (https://vimeo.com/8313889). Animation by
Hybrid Animation Medical. 21 December 2009.
Bacteriophages: What are they. Presentation by Professor Graham Hatfull, University of
Pittsburgh (https://www.youtube.com/watch?v=3VjE1zddXWk) on YouTube

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