Bacteriophage and bacteriophage typing

A bacteriophage, or phage, is a virus that infects a bacterial cell, taking over the host cell's genetic material, reproducing itself, and eventually destroying the bacterium. The word phage comes from the Greek word phagein, meaning "to eat." Bacteriophages have two main components, protein coat and a nucleic acid core of DNA or RNA . Most DNA phages have double-stranded DNA, whereas phage RNA may be double or single-stranded. The electron microscope shows that phages vary in size and shape. Filamentous or threadlike phages, discovered in 1963, are among the smallest viruses known. Scientists have extensively studied the phages that infect Escherichia coli (E.coli), bacteria that are abundant in the human intestine. Some of these phages, such as the T4 phage, consist of a capsid or head, often polyhedral in shape, that contains DNA, and an elongated tail consisting of a hollow core, a sheath around it, and six distal fibers attached to a base plate. When T4 attacks a bacterial cell, proteins at the end of the tail fibers and base plate attach to proteins located on the bacterial wall. Once the phage grabs hold, its DNA enters the bacterium while its protein coat is left outside.

Double stranded DNA phages reproduce in their host cells in two different ways: the lytic cycle and the lysogenic cycle. The lytic cycle kills the host bacterial cell. During the lytic cycle in E.coli, for example, the phage infects the bacterial cell, and the host cell commences to transcribe and translate the viral genes. One of the first genes that it translates encodes an enzyme that chops up the E.coli DNA. The host now follows instructions solely from phage DNA which commands the host to synthesize phages. At the end of the lytic cycle, the phage directs the host cell to produce the enzyme, lysozyme, that digests the bacterial cell wall. As a result, water enters the cell by osmosis and the cell swells and bursts. The destroyed or lysed cell releases up to 200 phage particles ready to infect nearby cells. On the other hand, the lysogenic cycle does not kill the bacterial host cell. Instead, the phage DNA is incorporated into the host cell's chromosome where it is then called a prophage. Every time the host cell divides, it replicates the prophage DNA along with its own. As a result, the two daughter cells each contain a copy of the prophage, and the virus has reproduced without harming the host cell. Under certain conditions, however, the prophage can give rise to active phages that bring about the lytic cycle.

In 1915, the English bacteriologist Frederick Twort (1877–1950) first discovered bacteriophages. While attempting to grow Staphylococcus aureus, the bacteria that most often cause boils in humans, he observed that some bacteria in his laboratory plates became transparent and died. Twort isolated the substance that was killing the bacteria and hypothesized that the agent was a virus. In 1917, the French-Canadian scientist Felix H. d'Hérelle independently discovered bacteriophages as well. The significance of this discovery was not appreciated, however, until about thirty years later when scientists conducted further bacteriophage research. One prominent scientist in the field was Salvador E. Luria (1912–1991), an Italian-American biologist especially interested in how x rays cause mutations in bacteriophages. Luria was also the first scientist to obtain clear images of a bacteriophage using an electron microscope. Salvador Luria emigrated to the United States from Italy and soon met Max Delbruck (1906–1981), a German-American molecular biologist. In the 1940s, Delbruck worked out the lytic mechanism by which some bacteriophages replicate. Together, Luria, Delbruck and the group of researchers that joined them studied the genetic changes that occur when viruses infect bacteria. Until 1952, scientists did not know which part of the virus, the protein or the DNA, carried the information regarding viral replication. It was then that scientists performed a series of experiments using bacteriophages. These experiments proved DNA to be the molecule that transmits the genetic information. (In 1953, the Watson and Crick model of DNA explained how DNA encodes information and replicates). For their discoveries concerning the structure and replication of viruses, Luria, Delbruck, and Hershey shared the Nobel Prize for physiology or medicine in 1969. In 1952, two American biologists, Norton Zinder and Joshua Lederberg at the University of Wisconsin, discovered that a phage can incorporate its genes into the bacterial chromosome. The phage genes are then transmitted from one generation to the next when the bacterium reproduces. In 1980, the English biochemist, Frederick Sanger, was awarded a Nobel Prize for determining the nucleotide sequence in DNA using bacteriophages.

In the last several decades, scientists have used phages for research. One use of bacteriophages is in genetic engineering, manipulating genetic molecules for practical uses. During genetic engineering, scientists combine genes from different sources and transfer the recombinant DNA into cells where it is expressed and replicated. Researchers often use E. coli as a host because they can grow it easily and the bacteria is well studied. One way to transfer the recombinant DNA to cells utilizes phages. Employing restriction enzymes to break into the phage's DNA, scientists splice foreign DNA into the viral DNA. The recombinant phage then infects the bacterial host. Scientists use this technique to create new medical products such as vaccines. In addition, bacteriophages provide information about genetic defects, human development, and disease. One geneticist has developed a technique using bacteriophages to manipulate genes in mice, while others are using phages to infect and kill disease-causing bacteria in mice. In addition, microbiologists found a filamentous bacteriophage that transmits the gene that encodes the toxin for cholera, a severe intestinal disease that kills tens of thousands worldwide each year.

See also Bacteria and bacterial infection; Biotechnology; Cell cycle (prokaryotic), genetic regulation of; Chromosomes, prokaryotic; Genetic regulation of prokaryotic cells; Laboratory techniques in microbiology; Phage genetics; Phage therapy; Viral genetics; Viral vectors in gene therapy; Virus replication; Viruses and responses to viral infection