Phage

From Free net encyclopedia

A phage (short for bacteriophage, from 'bacteria' and Greek phagein, meaning 'to eat') is a virus that infects bacteria. Like viruses that infect eukaryotes (plants, animals and fungi), phages display a variety of different compositions. Typically, they consist of an outer protein hull and the enclosed genetic material, which consists of double-stranded DNA of 5 to 650 kbp (kilo base pairs) in the vast majority of the phages known. The dimensions of a phage is on the order of 24 to 200 nm. Several phages sport a structure called tail, which is used to inject the genetic material into the host.

Phages are ubiquitous and can be found in many reservoirs populated by bacteria, such as soil or the intestine of animals. One of the densest natural sources for phages is seawater, where up to 2.5×10⁸ virions per cm³ have been found (see references).

Image:Tevenphage.png Image:Bacteriophage.jpg Image:Trialphage.jpg

1 Discovery and research
2 Life cycle
3 Therapy
4 Quotes
5 Model bacteriophages
6 See also
7 Resources

[edit]

Discovery and research

Phages were discovered independently in 1915 by Frederick Twort and in 1917 by Félix d'Herelle, who coined the name bacteriophage. Twort did not pursue the matter further, but d'Herelle went to Tbilisi in the Soviet Union, to continue the research on phages and phage therapy, where George Eliavi and he founded the still existing George Eliava Institute. Phages play an important role in molecular biology as cloning vectors to insert DNA into bacteria. Phage display is a test to screen for protein interactions by integrating multiple genes from a gene bank into phages.

[edit]

Life cycle

Phages infect only specific bacteria. It is unknown whether there is a phage for every species of bacteria as only a fraction of bacteria have been studied on this detail. Some phages are virulent, meaning that upon infecting a cell they immediately begin reproducing, and within a short time lyse (destroy) the cell, releasing new phages. Some phages (so-called temperate phages) can instead enter a relatively harmless state, either integrating their genetic material into the chromosomal DNA of the host bacterium (much like endogenous retroviruses in animals) or establishing themselves as plasmids. These endogenous phages, referred to as prophages, are then copied with every cell division together with the DNA of the host cell. They do not kill the cell, but monitor (via some proteins they code for) the status of their host. When the conditions of host worsen for instance due to increase in temperature or depletion of nutrients, the endogenous phages become active. They initiate the reproductive cycle resulting in the lysis of the host cell, thus pre-empting a possible demise of the bacterium. An example is phage λ of E. coli. Sometimes, prophages even provide benefit to the host bacterium while they are dormant, by adding new functions to the bacterial genome, a phenomenon called lysogenic conversion. A famous example is the conversion of a harmless strain of Vibrio cholerae by a phage into a highly virulent one, which causes cholera.

[edit]

Therapy

Phages were tried as anti-bacterial agents after their discovery. However Antibiotics, upon their discovery, proved to be more practical. Research on phage therapy was largely discontinued in the West. Phage therapy has been used since the 1940s in the former Soviet Union as an alternative to antibiotics for treating bacterial infections.

The evolution of bacterial strains through natural selection that are resistant to multiple drugs has led some medical researchers to re-evaluate phages as alternatives to the use of antibiotics. Unlike antibiotics, phages adapt along with the bacteria, as they have done for millions of years, so a sustained resistance is unlikely. A specific type of phage often infects only one specific type of bacterium (ranging from several species, to only certain subtypes within a species), so one has to make sure to identify the correct type of bacteria, which takes about 24 h. Sometimes mixes of several strains of phage are used to create a more 'broad spectrum' cure. An added advantage is that no other (possibly benevolent) bacteria are attacked (it effectively works as a very narrow spectrum antibiotic). However, this is a disadvantage in infections with several different types of bacteria, which is often the case. But when an effective phage has been found, it will seek out the bacteria (being a biological agent) and continue to kill bacteria of that type until they are all gone: this is unlike the action of antibiotics, which are chemotherapeutical.

Phages work best when in direct contact with the infection, so they are best applied directly to an open wound, which rarely is applicable in the current clinical setting where infections occur systemic. Despite individual successes in the former USSR where other therapies had failed, many researchers studying infectious diseases question whether phage therapy will achieve any medical relevance. There have been no large clinical trials to test the efficacy of phage therapy yet, but research continues because of the rise of multiple antibiotic resistance. A problem, though, is that they are attacked by the body's immune system.

[edit]