Difference between revisions of "Phage therapy"
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== Bacteriophages == | == Bacteriophages == | ||
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Bacteriophage (phage) is a virus that infects bacteria host cells. Viruses are | |||
acellular microbes that are obligate intracellular pathogens; requiring living cell | |||
hosts to carry out metabolic and reproductive needs. Bacteriophages carry with | |||
them a protein coat called a capsid that surrounds a small amount of DNA genetic | |||
material. The size of the DNA can vary from 5 genes to over 100 genes(1). The | |||
majority of the genes on phage DNA code for capsid proteins, proteins to protect | |||
viral DNA from degradation, and proteins used in the release from the host cell(1, | |||
2). Because phage cannot reproduce or undergo metabolism on their own, they | |||
must infect living bacteria cells in order to reproduce. As part of their reproductive | |||
cycle, phages kill the bacteria cell they are infecting. There are two main types of | |||
reproductive cycles that a phage can use: the lytic cycle and the lysogenic cycle. | |||
A typical phage lytic cycle consists of five main steps. The first step is | |||
attachment. The attachment occurs between the phage and a receptor or structure | |||
on the surface of the bacterial cell. Attachment is very specific for the | |||
bacteriophage, with each phage being able to only infect one species of bacteria. | |||
After attachment is entry and this is where the phage DNA enters into the cytoplasm | |||
of the bacteria cell. Once inside the bacteria cell, the phage takes over the metabolic | |||
machinery of the cell, degrades the bacteria DNA, and changes the cell into a phage | |||
producing factory. The viral DNA is translated and viral proteins are made in the | |||
synthesis part of the viral cycle. In addition to translation, viral DNA is also being | |||
replicated to produce more viral DNA. Once enough viral capsid proteins and viral | |||
DNA are synthesized, the assembly part of the cycle occurs. During assembly, the | |||
viral capsid proteins surround the viral DNA to build more bacteriophage. When | |||
enough bacteriophage particles have been assembled, the release phase occurs. | |||
During the release phase, the host cell lysis open, releasing numerous bacteriophage | |||
into the environment. The bacteriophage can then go and attach to another bacteria | |||
host cell to repeat the lytic cycle over and over again until no bacteria are available | |||
for attachment. | |||
Although the lytic cycle can occur with all bacteriophage, some phage can | |||
enter a dormant cycle called the lysogenic cycle. In the lysogenic cycle, attachment | |||
and entry still occur but the host cell DNA is not degraded upon entrance. Instead, | |||
the phage DNA incorporates into the host cell DNA to form a prophage. A prophage | |||
implies that a bacteriophage has infected the host cell and is in a dormant cycle. The | |||
length of this dormant cycle depends on a number of parameters such as, the | |||
specific bacteriophage, the host cell, and the stress of the environment. Most | |||
bacteria that enter this dormant stage never re-enter the lytic cycle. Each time the | |||
bacterial cell divides and replicates its DNA, the prophage DNA is also being | |||
replicated. Eventually induction occurs which is when the prophage excises out of | |||
the host DNA and re-enters the lytic cycle at the synthesis stage. During the | |||
synthesis phase, the host cell DNA is degraded and viral proteins are translated. | |||
The assembly and release phases will follow. Many things can trigger induction | |||
such as nutrient depletion, UV damage to host cell, or any change in environment | |||
temperature or pH(3). | |||
Bacteriophages provide a selective method for targeting and destroying | |||
specific bacteria. In addition, because bacteriophage cannot replicate without the | |||
presence of their host bacteria, once the bacteria have been eliminated, the viral | |||
particles will soon degrade and also be eliminated. For each bacteria that exists, | |||
there is at least one bacteriophage specifically able to attach and infect it. This | |||
makes bacteriophage the most abundant entity on earth an estimated 10^31 present | |||
on Earth(1). With such an abundance, this makes bacteriophage an excellent | |||
candidate for eliminating bacterial infections. | |||
== Questions and Specific Aims == | == Questions and Specific Aims == | ||
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