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bacteriophage

bacteriophage (băktēr´ēəfāj´), virus that infects bacteria and sometimes destroys them by lysis, or dissolution of the cell. Bacteriophages, or phages, have a head composed of protein, an inner core of nucleic acid—either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA)—and a hollow protein tail. A particular phage can usually infect only one or a few related species of bacteria; for example, coliphages are DNA-containing viruses that infect only the bacterium Escherichia coli.

A virus infects a bacterial cell by first attaching to the bacterial cell wall by its tail. In coliphages the tail is a complex protein structure consisting of a hollow contractile sheath, with a plate at the base that contains long protein fibers. The tail fibers fix the base plate to the specific receptor site on the bacterial cell wall, and the tail sheath contracts like a syringe, forcing the DNA that is inside the virus through the cell wall and cell membrane. The entire virus protein coat remains outside the bacterium.

The injected nucleic acid is the viral genetic material; it makes use of the bacterium's chemical energy and biosynthetic machinery to produce viral enzymes, as well as more phage nucleic acid. The viral proteins and nucleic acid molecules within the bacterial host assemble spontaneously into up to a hundred new phage particles. Eventually the bacterium lyses, releasing the particles. Lysis can be readily observed in bacteria growing on a solid medium, where groups of lysed cells appear as clear areas, or plaques.

Some DNA phages, called temperate phages, only lyse a small fraction of bacterial cells; in the remaining majority of the bacteria, the phage DNA becomes integrated into the bacterial chromosome and replicates along with it. In this state, known as lysogeny, the information contained in the viral nucleic acid is not expressed. A lysogenic bacterial culture can be treated with radiation or mutagens, inducing the cells to begin producing viruses and lyse. Lysogenic phages resemble bacterial genetic particles known as episomes. Incorporated phage genes are sometimes the source of the virulence of disease-causing bacteria.

The bacteriophage was discovered independently by the microbiologists F. W. Twort (1915) and Félix d'Hérelle (1917). The phages have been much used in the study of bacterial genetics and cellular control mechanisms largely because the bacterial hosts are so easily grown and infected with phage in the laboratory. Phages were also used in an attempt to destroy bacteria that cause epidemic diseases, but this approach was largely abandoned in the 1940s when antibacterial drugs became available. The possibility of "phage therapy" has recently attracted new interest among medical researchers, however, owing to the increasing threat posed by drug-resistant bacteria. In 2006 the Food and Drug Administration approved the use of bacteriophages that attack strains of Listeria as a food additive on ready-to-eat meat products.

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bacteriophage

bacteriophage (phage) A virus that is parasitic within a bacterium. Each phage is specific for only one type of bacterium. Most phages (virulent phages) infect, quickly multiply within, and destroy (lyse) their host cells. However, some (temperate phages) remain dormant in their hosts after initial infection: their nucleic acid becomes integrated into that of the host and multiplies with it, producing infected daughter cells (see lysogeny). Lysis may eventually be triggered by environmental factors. Phages are used experimentally to identify bacteria, to control manufacturing processes (such as cheese production) that depend on bacteria, and, because they can alter the genetic make-up of bacterial cells, they are important tools in genetic engineering as cloning vectors. See lambda phage.

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bacteriophage

bacteriophage (phage) (bak-teer-i-oh-fayj) n. a virus that attacks bacteria. The phage grows and replicates in the bacterial cell, which is eventually destroyed with the release of new phages. Each phage acts specifically against a particular species of bacterium. This is utilized in phage typing, a technique of identifying bacteria by the action of known phages on them.

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bacteriophage

bacteriophage (phage) A type of virus which infects bacteria. Infection with a bacteriophage may or may not lead to the death of the bacterium, depending on the phage and sometimes on conditions. A given bacteriophage usually infects only a single species or strain of bacterium. Phages can be found in most natural environments in which bacteria occur.

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bacteriophage

bacteriophage(phage) A type of virus which infects bacteria. Infection with a bacteriophage may or may not lead to the death of the bacterium, depending on the phage and sometimes on conditions. A given bacteriophage usually infects only a single species or strain of bacterium. Phages can be found in most natural environments in which bacteria occur.

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bacteriophage

bac·te·ri·o·phage / bakˈti(ə)rēəˌfāj/ • n. Biol. a virus that parasitizes a bacterium by infecting it and reproducing inside it.

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bacteriophage

bacteriophage Viruses that attack bacteria, commonly known as phages. They pass through bacterial filters, and can be a cause of considerable trouble in bacterial cultures (for example milk starter cultures).

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bacteriophage

bacteriophage Virus that lives on and infects bacteria. It has a protein head containing a core of DNA and a protein tail. Discovered in 1915, it is important in the study of genetics.

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Bacteriophage

Bacteriophage

Bacteriophage structure

Phages as valuable molecular tools

Resources

Bacteriophage (also known as phages) are viruses that target and infect only bacterial cells. The first observation of what turned out to be bacteriophage was made in 1896. Almost twenty years later, the British bacteriologist Frederick Twort (18771950) demonstrated that an unknown microorganism that could pass through a filter that excluded bacteria was capable of destroying bacteria. He did not explore this finding in detail, however. In 1915, the French Canadian micro-biologist Felix dHerelle observed the same result, and named the microorganism bacteriophage (bacteria eater, from the Greek phago, meaning to eat).

Many types of bacteriophage have been identified since their discovery in 1915, and they are named according to the type of bacteria they infect. For example, staphylophages are specific viruses of the staphylococcal bacteria, and coliphages specifically infect coliform bacteria.

Bacteriophage are the most thoroughly studied and well-understood viruses. They occur frequently in nature, carry out similar biological functions as other viruses, yet do not target human cells for infection. Phages have proven to be a valuable scientific research tool for a variety of applications: as models for the study of viral infectious mechanisms, as tools of biotechnology that introduce new genes into bacterial cells, and as potential treatments for human bacterial infection. For example, the experiments that lead to the

discovery of messenger ribonucleic acid, one of the keys to the manufacture of protein in bacteria, viruses, and even cells found in humans, were accomplished using a bacteriophage. Another example is the bacteriophage designated T4, which specifically infects the bacterium Escherichia coli. T4 has been a cornerstone of molecular biology; studies of the way T4 makes new copies of itself has revealed a great deal of information about bacteriophage genetics and the regulation of the expression the gene viral genetic material. Additionally, another bacteriophage, called lambda, has been fundamentally important to molecular biology as a model system for gene regulation and as a means of moving genetic material from one bacterium to another.

Bacteriophage structure

Bacteriophage have different three-dimensional shapes (or morphologies). Those that are known as T-even phages (i.e., T2, T4, and T6) have a shape similar to the Apollo spacecraft that landed on the Moon in the 1960s. These phages have a head that has a slightly spherical shape called an icosahedron. A tube connects the head to spider-like supporting legs. This overall shape is vital to the way T-even bacteriophage deliver their payload of genetic material into a bacterial cell. Once on the surface on a bacterium, the tube portion of the phage contracts, and the phage acts like microscopic hypodermic needles, literally injecting the genetic material into the bacterium.

Other bacteriophage can be spherical (e.g., PhiX174, S13) or long and threadlike (e.g., M13).

Structurally, bacteriophage, like most viruses, are composed of a protein coat surrounding a core containing DNA (deoxyribonucleic acid) or RNA (ribonucleic acid), though many variations on this basic design exist. The bacteria these viruses infect often measure about one micron in diameter (a micron is one thousandth of a millimeter) and the phages themselves may be as small as twenty-five thousandths of a micron. Bacteriophage infect their hosts by binding to the wall of the bacterial cell. The wall is perforated by enzyme action and phage DNA is injected into the cell. The genetic machinery of the cell is altered to make more bacteriophage DNA. Ultimately, the host cell dies when phage copies accumulate to the point of lysing (bursting) the cell membrane and releasing the phages, which go forth and continue the cycle.

Phages as valuable molecular tools

Much of what has been learned about the mechanisms of viral infection in general has been discerned through the study of bacteriophage. They have proved to be valuable molecular tools for biotechnology, as they can be used as vehicles to move genetic material from one organism into another organism.

It is through this revolutionary use of phages to introduce foreign DNA into new cells that human insulin was first safely and cheaply produced. In a process called lateral gene transfer, genes from one source are transplanted into a different living cell so that they will give the different cell a new characteristic (found in the first cell). For example, specific human genes are implanted in bacterial cells with the aid of phages that allow bacterial cells to produce human insulin and other valuable protein products in great purity and quantity. Lateral gene transfer has given a new, human characteristic to bacterial cells. Bacteriophage act as the deliverers of transferred genes.

Today, bacteriophage used to inject DNA into host cells for research or biotechnology can be manufactured in test tubes. Kits containing bacteriophage proteins and structural components are used to create intact phages from pieces that spontaneously self-assemble under the right chemical conditions. In this way, scientists can customize bacteriphage and the DNA they contain for many uses.

Additionally, bacteriophage are only now beginning to fulfill the dream of Felix dHerelle, in combating infection in humans and animals. The medical potential of many bacteriophage is great as a treatment for blood infection and meningitis for example, along with a host of bacterial infections increasingly resistant to antibiotics.

Bacteriophage therapy is also being explored as a means of curbing bacterial diseases without the use of antibiotics. While antibiotic resistance is possible and,

KEY TERMS

Bacteriophage A virus that infects bacteria.

Icosahedron A 20sided polyhedron.

indeed, is occurring at greater frequency over time, resistance to bacteriophages is remote. Originally explored at the Eliava Institute of Bacteriophage, Microbiology, and Virology in the Russian Republic of Georgia over 70 years ago, bacteriophage therapy fell into disfavor. However, research interest was rekindled in the 1990s. As of 2006, bacteriophage therapy still remains experimental. However, its benefits and potential are promising.

See also Ebola virus; Epstein-Barr virus; Retrovirus.

Resources

BOOKS

Abedon, Stephen T., and Richard L. Calendar. The Bacteriophages. Oxford: Oxford University Press, 2005.

Hausler, Thomas. Viruses vs. Superbugs: A Solution to the Antiiotics Crisis? New York: MacMillan, 2006.

Kutter, Elizabeth, and Alexander Sulakvekidze. Bacteriophages: Biology and Applications. Boca Raton: CRC, 2004.

Brian Hoyle

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Bacteriophage

Bacteriophage

Bacteriophage (also known as phages) are viruses that target and infect only bacterial cells. The first observation of what since turned out to be bacteriophage was made in 1896. Almost twenty years later, the British bacteriologist Frederick Twort demonstrated that an unknown microorganism that could pass through a filter that excluded bacteria was capable of destroying bacteria. He did not explore this finding in detail, however. In 1915, the French Canadian microbiologist Felix d'Herelle observed the same result, and named the microorganism bacteriophage (bacteria eater, from the Greek phago, meaning to eat).

Many types of bacteriophage have been identified since their discovery in 1915, and they are named according to the type of bacteria they infect. For example, staphylophages are specific viruses of the staphylococcal bacteria, and coliphages specifically infect coliform bacteria.

Bacteriophage are the most thoroughly studied and well-understood viruses. They occur frequently in nature, carry out similar biological functions as other viruses, yet do not target human cells for infection . Phages have proven to be a valuable scientific research tool for a variety of applications: as models for the study of viral infectious mechanisms, as tools of biotechnology that introduce new genes into bacterial cells, and as potential treatments for human bacterial infection. For example, the experiments that lead to the discovery of messenger ribonucleic acid , one of the keys to the manufacture of protein in bacteria, viruses, and even cells found in humans, were accomplished using a bacteriophage. Another example is the bacteriophage designated T4, which specifically infects the bacterium Escherichia coli . T4 has been a cornerstone of molecular biology ; studies of the way T4 makes new copies of itself has revealed a great deal of information about bacteriophage genetics and the regulation of the expression the gene viral genetic material. Additionally, another bacteriophage, called lambda, has been fundamentally important to molecular biology as a model system for gene regulation and as a means of moving genetic material from one bacterium to another.


Bacteriophage structure

Bacteriophage have different three-dimensional shapes (or morphologies). Those that are known as T-even phages (i.e., T2, T4, and T6) have a shape similar to the Apollo spacecraft that landed on the Moon in the 1960s. These phages have a head that has a slightly spherical shape called an icosahedron. A tube connects the head to spider-like supporting legs. This overall shape is vital to the way T-even bacteriophage deliver their payload of genetic material into a bacterial cell . Once on the surface on a bacterium, the tube portion of the phage contracts, and the phage acts like microscopic hypodermic needles, literally injecting the genetic material into the bacterium.

Other bacteriophage can be spherical (e.g. PhiX174, S13) or long and thread-like (e.g., M13).

Structurally, bacteriophage, like most viruses, are composed of a protein coat surrounding a core containing DNA (deoxyribonucleic acid ) or RNA (ribonucleic acid), though many variations on this basic design exist. The bacteria these viruses infect often measure about one micron in diameter (a micron is one thousandth of a millimeter) and the phages themselves may be as small as twenty-five thousandths of a micron. Bacteriophage infect their hosts by binding to the wall of the bacterial cell. The wall is perforated by enzyme action and phage DNA is injected into the cell. The genetic machinery of the cell is altered to make more bacteriophage DNA. Ultimately, the host cell dies when phage copies accumulate to the point of lysing (bursting) the cell membrane and releasing the phages, which go forth and continue the cycle.

Phages as valuable molecular tools

Much of what has been learned about the mechanisms of viral infection in general has been discerned through the study of bacteriophage. They have proved to be valuable molecular tools for biotechnology, as they can be used as vehicles to move genetic material from one organism into another organism.

It is through this revolutionary use of phages to introduce foreign DNA into new cells that human insulin was first safely and cheaply produced. In a process called lateral gene transfer, genes from one source are transplanted into a different living cell so that they will give the different cell a new characteristic (found in the first cell). For example, specific human genes are implanted in bacterial cells with the aid of phages that allow bacterial cells to produce human insulin and other valuable protein products in great purity and quantity. Lateral gene transfer has given a new, human characteristic to bacterial cells. Bacteriophage act as the deliverers of transferred genes.

Today, bacteriophage used to inject DNA into host cells for research or biotechnology can be "manufactured" in test tubes. Kits containing bacteriophage proteins and structural components are used to create intact phages from pieces that spontaneously self-assemble under the right chemical conditions. In this way, scientists can customize bacteriphage and the DNA they contain for many uses.

Additionally, bacteriophage are only now beginning to fulfill the dream of Felix d'Herelle, in combating infection in humans and animals. The medical potential of many bacteriophage is great as a treatment for blood infection and meningitis for example, along with a host of bacterial infections increasingly resistant to antibiotics .

See also Ebola virus; Epstein-Barr virus; Retrovirus.


Resources

books

Flint, S.J., L.W. Enquist, R.M. Krug, et al. Principles of Virology: Molecular Biology, Pathogenesis, and Control. Washington, DC: American Society for Microbiology Press, 1999.

Stahl, F.W. We Can Sleep Later: Alfred D. Hershey and theOrigins of Molecular Biology. Cold Spring Harbor, NY: Cold Spring Harbor Press, 2000.

Summers, W.C. Felix d'Herelle and the Origins of MolecularBiology. New Haven: Yale University Press, 2000.


Brian Hoyle

KEY TERMS

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Bacteriophage

—A virus that infects bacteria.

Icosahedron

—A 20–sided polyhedron.

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