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
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.
for attachment.
 
<br/>
Although the lytic cycle can occur with all bacteriophage, some phage can
: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).
 
<br/>
enter a dormant cycle called the lysogenic cycle. In the lysogenic cycle, attachment
: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 1x10^31 present on Earth(1). With such an abundance, this makes bacteriophage an excellent candidate for eliminating bacterial infections.
 
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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