Bacterial host cells are not defenceless against phage attack. The heavy burden put on the susceptible bacteria may select cell variants that are refractory to bacteriophage infection (bacteriophage insensitive mutants, BIMs). This is usually accomplished by loss, modification,or masking of the bacteriophage receptors located at the cell wall.
A number of strategies that may be used to overcome or limit resistance development have been indicated in the literature, including the prevention of the recycling of the bacteriophages in the reservoir of the pathogen by alternating use of different bacteriophages (either in a cocktail of several bacteriophages, or in consecutive treatments).
Bacteriophages generally exhibit a narrow host range, which is usually restricted to one genus of bacteria but more frequently restricted to either a limited number of species within a genus or to a limited number of bacterial strains within a species .
The best virulent bacteriophages for Phage Terapy applications are those with the broadest possible host range. These are termed polyvalent bacteriophages or WHR (wide host range) bacteriophages as they are usually active against many species within a bacterial genus.
Phage Therapy
a)when we do not know if the bacterial infection is caused by one bacterium or by two or three bacteria and when we have very little time.
Phage Therapy administration:
Bacteriophage composition (cocktail of 4 or 8 or 10 different Phages; cocktail of 6 or 9 or 12 different Phages)
b)when we have time and when we know the bacterial cause of infection.
If the infection is caused by bacteria:
Phage Therapy administration:
Bacteriophage composition (cocktail of 4 or 8 or 10 different Phages; cocktail of 6 or 9 or 12 different Phages)
If the infection is caused by one bacterium:
Phage Therapy administration:
Bacteriophage composition (cocktail of 2 different Phages; cocktail of 3 different Phages; cocktail of 4 different Phages)
The Temporariness's Principle
The Effectiveness of Bacteriophage compositions is conditioned by the Temporariness's Principle:
"The Effectiveness of Bacteriophage compositions ready to use, when they are used in Phage Therapy, must be tested frequently. Both Host range and Virulence of any Bacteriophage composition must be unchanged when it is compared to respective original composition".
Each Bacteriophage composition is designed to match regional strains of bacteria for different infections in different parts of the body. We must test the sensitivity of phages to dominant strains of bacteria every 5-6 months. The Phage cocktail is updated by adding new phages or removing old ones to attack newly emerging strains.
It is important to understand that the precise properties exhibited by one bacteriophage cannot be assumed to be identical for other bacteriophages. Each bacteriophage will have its own characteristic properties including host range, burst size, and ability to maintain its physical integrity in different environments.
