Difference between revisions of "Phage therapy"

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== Bacteriophages ==
== Bacteriophages ==
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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