Bacteriophage

A bacteriophage (/bækˈtɪərioʊfeɪdʒ/), also known informally as a phage (/feɪdʒ/), is a virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν (phagein), "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.

Bacteriophages are among the most common and diverse entities in the biosphere.[1] Bacteriophages are ubiquitous viruses, found wherever bacteria exist. It is estimated there are more than 1031 bacteriophages on the planet, more than every other organism on Earth, including bacteria, combined.[2] One of the densest natural sources for phages and other viruses is seawater, where up to 9x108 virions per millilitre have been found in microbial mats at the surface,[3] and up to 70% of marine bacteria may be infected by phages.[4]

Phages have been used for more than 90 years as an alternative to antibiotics in the former Soviet Union and Central Europe, as well as in France.[5] They are seen as a possible therapy against multi-drug-resistant strains of many bacteria (see phage therapy).[6] 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.[7]

PhageExterior
The structure of a typical myovirus bacteriophage
11 Hegasy Phage T4 Wiki E CCBYSA
Anatomy and infection cycle of phage T4

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.

Nineteen families are currently recognized by the ICTV that infect bacteria and archaea. Of these, only two families have RNA genomes, and only five families are surrounded by an envelope. Of the viral families with DNA genomes, only two have single-stranded genomes. Eight of the viral families with DNA genomes have circular genomes, while nine have linear genomes. Nine families infect bacteria only, nine infect archaea only, and one (Tectiviridae) infects both bacteria and archaea.

Bacteriophage P22 Casjens Lenk
Bacteriophage P22, a member of the Podoviridae by morphology due to its short, non-contractile tail
ICTV classification of prokaryotic (bacterial and archaeal) viruses[1]
Order Family Morphology Nucleic acid Examples
Caudovirales Ackermannviridae Nonenveloped, contractile tail Linear dsDNA
Myoviridae Nonenveloped, contractile tail Linear dsDNA T4, Mu, P1, P2
Siphoviridae Nonenveloped, noncontractile tail (long) Linear dsDNA λ, T5, HK97, N15
Podoviridae Nonenveloped, noncontractile tail (short) Linear dsDNA T7, T3, Φ29, P22
Ligamenvirales Lipothrixviridae Enveloped, rod-shaped Linear dsDNA Acidianus filamentous virus 1
Rudiviridae Nonenveloped, rod-shaped Linear dsDNA Sulfolobus islandicus rod-shaped virus 1
Unassigned Ampullaviridae Enveloped, bottle-shaped Linear dsDNA
Bicaudaviridae Nonenveloped, lemon-shaped Circular dsDNA
Clavaviridae Nonenveloped, rod-shaped Circular dsDNA
Corticoviridae Nonenveloped, isometric Circular dsDNA PM2
Cystoviridae Enveloped, spherical Segmented dsRNA
Fuselloviridae Nonenveloped, lemon-shaped Circular dsDNA
Globuloviridae Enveloped, isometric Linear dsDNA
Guttaviridae Nonenveloped, ovoid Circular dsDNA
Inoviridae Nonenveloped, filamentous Circular ssDNA M13
Leviviridae Nonenveloped, isometric Linear ssRNA MS2,
Microviridae Nonenveloped, isometric Circular ssDNA ΦX174
Plasmaviridae Enveloped, pleomorphic Circular dsDNA
Pleolipoviridae Enveloped, pleomorphic Circular ssDNA, circular dsDNA, or linear dsDNA
Portogloboviridae Enveloped, isometric Circular dsDNA
Sphaerolipoviridae Enveloped, isometric Linear dsDNA
Spiraviridae Nonnveloped, rod-shaped Circular ssDNA
Tectiviridae Nonenveloped, isometric Linear dsDNA
Tristromaviridae Enveloped, rod-shaped Linear dsDNA
Turriviridae Enveloped, isometric Linear dsDNA

It has been suggested that members of Picobirnaviridae infect bacteria, but not mammals.[8]

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.[9] 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 [10]

Twort's research was interrupted by the onset of World War I and a shortage of funding.

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."[11] 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.[12] It was D'Herelle who conducted much research into bacteriophages and introduced the concept of phage therapy.[13]

More than a half a century later, 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.[14]

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.[15]
  • 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 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.[16] 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.[16] 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.[17] 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.[17]

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.[3][4][5] 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.[18]

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.[19] 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.[20]

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."[21] This includes rivers traditionally thought to have healing powers, including India's Ganges River.[22]

Other

Food industry - 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.[23] In July 2007, the same bacteriophage were approved for use on all food products.[24] In 2011 USDA confirmed that LISTEX is a clean label processing aid and is included in USDA.[25] 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.

Dairy industry - Bacteriophages present in the environment can cause fermentation failures of cheese starter cultures. In order to avoid this, mixed-strain starter cultures and culture rotation regimes can be used.[26]

Diagnostics - In 2011, the FDA cleared the first bacteriophage-based product for in vitro diagnostic use.[27] 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.[28]

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.[29] 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[17] 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.[30]

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.[31]

Antimicrobial drug discovery - Phage proteins often have antimicrobial activity and may serve as leads for peptidomimetics, i.e. drugs that mimic peptides.[32] 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.[33]

Basic research - Bacteriophages are important model organisms for studying principles of evolution and ecology.[34]

Replication

Phage injection
Diagram of the DNA injection process

Bacteriophages may have a lytic cycle or a lysogenic cycle, and a few viruses are capable of carrying out both. 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 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.[35]

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.[36][37] Strategies to combat certain bacterial infections by targeting these toxin-encoding prophages have been proposed.[38]

Attachment and penetration

Phage
In this electron micrograph of bacteriophages attached to a bacterial cell, the viruses are the size and shape of coliphage T1

To enter a host cell, bacteriophages attach 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. Host growth conditions also influence the ability of the phage to attach and invade them.[39] 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 making contact with 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,[4] injecting genetic material through the bacterial membrane. The injection is acomplished 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 similar to 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 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.[40] Some dsDNA bacteriophages encode ribosomal proteins, which are thought to modulate protein translation during phage infection.[41]

Virion assembly

In the case of the T4 phage, the construction of new virus particles involves the assistance of helper proteins. 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. The DNA is packed efficiently within the heads. The whole process takes about 15 minutes.

Tevenphage
Diagram of a typical tailed bacteriophage structure

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.

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.[42]

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).[43] 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.[44]

Systems biology

Phage often have dramatic effects on their hosts. As a consequence, the transcription pattern of the infected bacterium may change considerably. 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.[45]

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 31 interactions. However, a large-scale study revealed 62 interactions, most of which were new. 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.[46]

In the environment

Metagenomics has allowed the in-water detection of bacteriophages that was not possible previously.[47]

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.[48] Non-polluted water may contain approximately 2×108 bacteriophages per mL.[49]

Bacteriophages are thought to contribute extensively to horizontal gene transfer in natural environments, principally via transduction, but also via transformation.[50] Metagenomics-based studies also have revealed that viromes from a variety of environments harbor antibiotic-resistance genes, including those that could confer multidrug resistance.[51]

Model bacteriophages

The following bacteriophages are extensively studied:

See also

References

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External links

Bacteriophage MS2

The bacteriophage MS2 is an icosahedral, positive-sense single-stranded RNA virus that infects the bacterium Escherichia coli and other members of the Enterobacteriaceae. MS2 is a member of a family of closely related bacterial viruses that includes bacteriophage f2, bacteriophage Qβ, R17, and GA.

Caudovirales

The Caudovirales are an order of viruses also known as the tailed bacteriophages (cauda is Latin for "tail"). Under the Baltimore classification scheme, the Caudovirales are group I viruses as they have double stranded DNA (dsDNA) genomes, which can be anywhere from 18,000 base pairs to 500,000 base pairs in length. The virus particles have a distinct shape; each virion has an icosahedral head that contains the viral genome, and is attached to a flexible tail by a connector protein. The order encompasses a wide range of viruses, many containing genes of similar nucleotide sequence and function. However, some tailed bacteriophage genomes can vary quite significantly in nucleotide sequence, even among the same genus. Due to their characteristic structure and possession of potentially homologous genes, it is believed these bacteriophages possess a common origin.There are at least 350 recognised species in this order.

Corticovirus

Corticovirus is a genus of viruses in the family Corticoviridae. Corticoviruses are bacteriophages; that is, their natural hosts are bacteria. The genus contains only one species, the type species Pseudoalteromonas virus PM2 (also known as Pseudoalteromonas phage PM2 or bacteriophage PM2). The name is derived from Latin cortex, corticis (meaning 'crust' or 'bark'). However, prophages closely related to PM2 are abundant in the genomes of aquatic bacteria, suggesting that the ecological importance of corticoviruses might be underestimated. Bacteriophage PM2 was first described in 1968 after isolation from seawater sampled from the coast of Chile.

Cystovirus

Cystovirus is a genus of viruses, in the family Cystoviridae. Pseudomonas syringae pathovar phaseolicola bacteria serve as natural hosts. There is currently only one species in this genus: the type species Pseudomonas phage phi6.

Enterobacteria phage T2

Enterobacteria phage T2 is a virus that infects and kills E. coli. It is in the genus T4virus, and the family Myoviridae. Its genome consists of linear double-stranded DNA, with repeats at either end. The phage is covered by a protective protein coat.

The T2 phage can quickly turn an E. coli cell into a T2-producing factory that releases phages when the cell ruptures. Experiments conducted in 1952 by Alfred Hershey and Martha Chase demonstrated how the DNA of viruses is injected into the bacterial cells, while most of the viral proteins remain outside. The injected DNA molecules cause the bacterial cells to produce more viral DNA and proteins. These discoveries supported that DNA, rather than proteins, is the hereditary material.

The first phages that were studied in detail included seven that commonly infect E. coli. They were named Type 1 (T1), Type 2 (T2), etc., for easy reference, however, due to structural similarities between the T2, T4, and T6 bacteriophages, they are now commonly referred to as T-Even phages.

The phage can attach to the surface of a bacterium using the proteins on its 'feet' (tail fibers), and inject its genetic material (either, but not both, DNA or RNA). This genetic material uses the host cell's ribosomes to replicate, and synthesize proteins for the capsid and tail of the phage. New phages are assembled within the cell until the cellular membrane lyses (splits open). The newly made phages are now free to attack more cells. This is the Lytic cycle.

Escherichia virus T4

Escherichia virus T4 is a species of bacteriophages that infect Escherichia coli bacteria. It is a member of virus subfamily Tevenvirinae (not to be confused with T-even bacteriophages, which is an alternate name of the species) and includes among other strains (or isolates) Enterobacteria phage T2, Enterobacteria phage T4 and Enterobacteria phage T6. T4 is capable of undergoing only a lytic lifecycle and not the lysogenic lifecycle.

Inoviridae

Inoviridae is a family of bacteriophage viruses. The genomes are composed of circular single-stranded DNA. Bacteria serve as natural hosts. There are, as of 2014, 43 defined species in this family, divided between two genera.

Lambda phage

Enterobacteria phage λ (lambda phage, coliphage λ, officially Escherichia virus Lambda) is a bacterial virus, or bacteriophage, that infects the bacterial species Escherichia coli (E. coli). It was discovered by Esther Lederberg in 1950 when she noticed that streaks of mixtures of two E. coli strains, one of which treated with ultraviolet light, was "nibbled and plaqued". The wild type of this virus has a temperate lifecycle 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); mutant strains are unable to lysogenize cells – instead, they grow and enter the lytic cycle after superinfecting an already lysogenized cell.The phage particle consists of a head (also known as a capsid), a tail, and tail fibers (see image of virus below). The head contains the phage's double-strand linear DNA genome. During infection, the phage particle recognizes and binds to its host, E. coli, causing DNA in the head of the phage to be ejected through the tail into the cytoplasm of the bacterial cell. Usually, a "lytic cycle" ensues, where the lambda DNA is replicated and new phage particles are produced within the cell. This is followed by cell lysis, releasing the cell contents, including virions that have been assembled, into the environment. However, under certain conditions, the phage DNA may integrate itself into the host cell chromosome in the lysogenic pathway. In this state, the λ DNA is called a prophage and stays resident within the host's genome without apparent harm to the host. The host is termed a lysogen when a prophage is present. This prophage may enter the lytic cycle when the lysogen enters a stressed condition.

Lysis

Lysis ( LY-sis; Greek λύσις lýsis, "a loosing" from λύειν lýein, "to unbind") refers to the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" LIT-ək) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a lysate. In molecular biology, biochemistry, and cell biology laboratories, cell cultures may be subjected to lysis in the process of purifying their components, as in protein purification, DNA extraction, RNA extraction, or in purifying organelles.

Many species of bacteria are subject to lysis by the enzyme lysozyme, found in animal saliva, egg white, and other secretions. Phage lytic enzymes (lysins) produced during bacteriophage infection are responsible for the ability of these viruses to lyse bacterial cells. Penicillin and related β-lactam antibiotics cause the death of bacteria through enzyme-mediated lysis that occurs after the drug causes the bacterium to form a defective cell wall. If the cell wall is completely lost and the penicillin was used on gram-positive bacteria, then the bacterium is referred to as a protoplast, but if penicillin was used on gram-negative bacteria, then it is called a spheroplast.

M13 bacteriophage

M13 is a virus that infects the bacterium Escherichia coli. It is composed of a circular single-stranded DNA molecule encased in a thin flexible tube made up of about 2700 copies of the major coat protein, P8. The ends of the tube are capped with minor coat proteins. Infection starts when the minor coat protein P3 attaches to the receptor at the tip of the F pilus of the bacterium. Infection with M13 is not lethal; however, the infection causes turbid plaques in E. coli because infected bacteria grow more slowly than the surrounding uninfected bacteria. It engages in a viral lifestyle known as a chronic infection which is neither lytic nor temperate. However a decrease in the rate of cell growth is seen in the infected cells. M13 plasmids are used for many recombinant DNA processes, and the virus has also been studied for its uses in nanostructures and nanotechnology.

Marine bacteriophage

Marine bacteriophages or marine phages are viruses that live as obligate parasitic agents in marine bacteria such as cyanobacteria. Their existence was discovered through electron microscopy and epifluorescence microscopy of ecological water samples, and later through metagenomic sampling of uncultured viral samples. Marine phages, although microscopic and essentially unnoticed by scientists until recently, appear to be the most abundant and diverse form of DNA replicating agent on the planet. There are approximately 4x1030 phage in oceans or 5x107 per millilitre. Quantification of marine viruses was originally performed using transmission electron microscopy but has been replaced by epifluorescence or flow cytometry.

Microviridae

Microviridae is a family of bacteriophages with a single-stranded DNA genome. The name of this family is derived from the ancient Greek word μικρός (mikrós), meaning "small". This refers to the size of their genomes, which are among the smallest of the DNA viruses. Enterobacteria, intracellular parasitic bacteria, and spiroplasma serve as natural hosts. There are currently 12 species in this family, divided among 7 genera and one subfamily.

Phage ecology

Bacteriophages (phages), potentially the most numerous "organisms" on Earth, are the viruses of bacteria (more generally, of prokaryotes). Phage ecology is the study of the interaction of bacteriophages with their environments.

Phage therapy

Phage therapy or viral phage therapy is the therapeutic use of bacteriophages to treat pathogenic bacterial infections. Phage therapy has many potential applications in human medicine as well as dentistry, veterinary science, and agriculture. If the target host of a phage therapy treatment is not an animal, the term "biocontrol" (as in phage-mediated biocontrol of bacteria) is usually employed, rather than "phage therapy".

Bacteriophages are much more specific than antibiotics. They are typically harmless not only to the host organism, but also to other beneficial bacteria, such as the gut flora, reducing the chances of opportunistic infections. They have a high therapeutic index, that is, phage therapy would be expected to give rise to few side effects. Because phages replicate in vivo (in cells of living organism), a smaller effective dose can be used.

This specificity is also a disadvantage: a phage will kill a bacterium only if it matches the specific strain. Consequently, phage mixtures ("cocktails") are often used to improve the chances of success. Alternatively, samples taken from recovering patients sometimes contain appropriate phages that can be grown to cure other patients infected with the same strain.

Phages tend to be more successful than antibiotics where there is a biofilm covered by a polysaccharide layer, which antibiotics typically cannot penetrate. In the West, no therapies are currently authorized for use on humans.Phages are currently being used therapeutically to treat bacterial infections that do not respond to conventional antibiotics, particularly in Russia and Georgia. There is also a phage therapy unit in Wrocław, Poland, established 2005, the only such centre in a European Union country.

Phagemid

A phagemid or phasmid is a DNA-based cloning vector, which has both bacteriophage and plasmid properties. These vectors carry, in addition to the origin of plasmid replication, an origin of replication derived from bacteriophage. Unlike commonly used plasmids, phagemid vectors differ by having the ability to be packaged into the capsid of a bacteriophage, due to their having a genetic sequence that signals for packaging. Phagemids are used in a variety of biotechnology applications; for example, they can be used in a molecular biology technique called "Phage Display".

Phi X 174

The phi X 174 (or ΦX174) bacteriophage is a single-stranded DNA (ssDNA) virus that infects Escherichia coli, and the first DNA-based genome to be sequenced. This work was completed by Fred Sanger and his team in 1977. In 1962, Walter Fiers and Robert Sinsheimer had already demonstrated the physical, covalently closed circularity of ΦX174 DNA. Nobel prize winner Arthur Kornberg used ΦX174 as a model to first prove that DNA synthesized in a test tube by purified enzymes could produce all the features of a natural virus, ushering in the age of synthetic biology. In 1972-1974, Jerard Hurwitz, Sue Wickner, and Reed Wickner with collaborators identified the genes required to produce the enzymes to catalyze conversion of the single stranded form of the virus to the double stranded replicative form. In 2003, it was reported by Craig Venter's group that the genome of ΦX174 was the first to be completely assembled in vitro from synthesized oligonucleotides. The ΦX174 virus particle has also been successfully assembled in vitro. Recently, it was shown how its highly overlapping genome can be fully decompressed and still remain functional.

T7 DNA polymerase

T7 DNA polymerase is an enzyme used during the DNA replication of the T7 bacteriophage. During this process, the DNA polymerase “reads” existing DNA strands and creates two new strands that match the existing ones. The T7 DNA polymerase requires a host factor, E. coli thioredoxin, in order to carry out its function. This helps stabilize the binding of the necessary protein to the primer-template to improve processivity by more than 100-fold, which is a feature unique to this enzyme. It is a member of the Family A DNA polymerases, which include E. coli DNA polymerase I and Taq DNA polymerase.

This polymerase has various applications in site-directed mutagenesis as well as a high-fidelity enzyme suitable for PCR. It has also served as the precursor to Sequenase, an engineered-enzyme optimized for DNA sequencing.

T7 phage

Bacteriophage T7 (or the T7 phage) is a bacteriophage, a virus that infects susceptible bacterial cells, that is composed of DNA and infects most strains of Escherichia coli. Bacteriophage T7 has a lytic life cycle and several properties that make it an ideal phage for experimentation.

Tectivirus

Tectiviridae is a family of viruses with three genera. Gram-negative bacteria serve as natural hosts. There are currently four species in this genus including the type species Enterobacteria phage PRD1. Tectiviruses have no head-tail structure, but are capable of producing tail-like tubes of ~ 60×10 nm upon adsorption or after chloroform treatment. The name is derived from Latin tectus (meaning 'covered').

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