information

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Phage therapy is influenced by:

Phage therapy is influenced by:

Country :
the epidemiological situation is different from country to country in terms of circulating bacteria and bacteriophages. Example: a lytic phages from Italy may be no active on the same bacteria (genus and species) isolated from another country and vice versa.
Chronolability
Mutation rate
Phenotypical delay
Phage cocktail
My point of view

From Wikipedia


If the target host* of a phage therapy treatment is not
an animal the term "
biocontrol" (as in phage-mediated biocontrol of bacteria) is usually employed, rather than "phage therapy".

"In silico"

From:"Genomics,Proteomics and Clinical Bacteriology", N.Woodford and Alan P.Johnson

Phrase that emphasizes the fact that many molecular biologists spend increasing amounts of their time in front of a computer screen, generating hypotheses that can subsequently be tested and (hopefully) confirmed in the laboratory.

Sunday, 29 June 2014

Differentiation of Bacteriophages on the basis of their Life Cycle





The differentiation between phages on the basis of their type of genetic material is a rather technical one. Another important differentiation can be made on the basis of the Phage Life Cycle.

Two main groups are distinguished there:

Lysogenic or Temperate PhagesLytic Phages




Lysogenic phages

The most important feature of lysogenic phages is the integration of their genome in the bacterial genome after infection.
This results in the so-called pro-phage stage.
Genes that control the lytic pathway are repressed by protein repressors which bind to specific DNA-regions. This prevents
transcription of genes whose products are involved in the lytic pathway. During this stage the bacteria grow and divide normally and the phage inside the bacteria can remain unnoticed.

Upon activation of the pro-phage, in many cases for as yet unknown reasons, the bacteriophages genetic material is transcribed and replicated inside the bacterium. This ultimately results in
the formation of new bacteriophage particles which, once released form the bacterium, are capable of infecting new bacteria and integration of their genetic material into the bacterial genome, thus closing the circle.
Prophages are released by excision. Sometimes excision is not precise and bacterial genes adjacent to the prophage are packaged into a phage particle. These bacterial genes then can be transferred into other percipient bacteria and during, the formation of the prophage stage, integrated into the chromosome.

This process is called Transduction and has not
only led to the exchange of bacterial DNA between bacteria but also to the transfer of bacterial DNA to the genome of certain phages.
A nice example of this is the presence of so-called ‘pathogenicity islands’ in the genome of CTX Phi phage of the
Vibrio cholerae (cholera bacterium) which contains a bacterial toxin encoding gene.

Although highly interesting, lysogenic phages are (as yet) unpredictable in their properties and behaviour. Transition from the pro-phage stage to the lytic phage is uncontrollable and the exchange of genetic material unpredictable.
Lysogenic phages have been observed to transfer potentially harmful genes into their target bacteria (including genes encoding Shiga toxins of Shigatoxinogenic E. coli , the cholera toxin of toxinogenic Vibrio cholerae, and various antibiotic resistance genes.

Although many of the lysogenic phages are relatively well studied (e.g. Phage λ) and sometimes detailed knowledge is available about their genome and its regulation, because of their unpredictable behaviour, they are generally considered to be unsuitable of use in bacteriophage therapy.



Lytic phages

Lytic phages infect their host, replicate and then kill their host by cell lysis, thereby releasing progeny viruses into the environment.

Infection of the bacterial host is often based on specific recognition of particular components (receptors)
on the pili or cell wall of the bacterium which is likely to determine the specific recognition. After initial infection it can be a matter of hours before cell lysis occurs.

Lytic phages are theoretically ideally suited as an alternative antibiotic in phage therapy:

Most bacteriophages are very specific for their host bacterium.

• Upon successful infection they replicate exponentially.

• They kill their hosts quickly (often in hours).

• Upon bacterial lysis a large number of progeny phages are released into the environment.Each of those phages is capable of infecting other target bacteria. As an ‘antibioticbacteriophages are ‘self multiplying’.

Bacteriophages depend on their hosts and will disappear with the destruction of their target bacterium leaving no residues;
antibiotic’bacteriophages are ‘self eliminating’.