Bacteriophage Therapy has a contentious history
Bacteriophages are bacteria-specific viruses, which play a crucial role in regulating bacterial populations in nature. The use of bacteriophage to treat bacterial infections started long before the discovery of penicillin, the first true antibiotic.
It goes without saying that at the time of the discovery of bacteriophage therapy even the existence of bacteriophage was a topic of dispute until after the evolution of electronic microscopy.
From that time on, a number of logistical and technical obstacles in its implementation, along with the inconsistent success stories and the successful advancement of antibiotic treatment have led to its abandonment in the United States and Western Europe. Bacteriophage Therapy continued to develop and refined in the former USSR and Poland. Ultimately, it took the severities of antibiotic resistance to force the western world to look back at the bacteriophage therapy.
Biology and Lifecycle of Bacteriophage
Bacteriophages consist of DNA or RNA encapsulated within a protein capsid. Being parasitic in nature, these are dependent on a bacterial host for survival and reproduction.
The first step of the bacteriophage-bacteria interaction is the attachment of the bacteriophage to the specific receptors of the bacterial cell wall.
Upon attaching itself to the specific receptors, the Bacteriophages induce a pore in the bacterial cell wall, and inject their genome into the host cell, leaving its viral capsid outside of the bacteria.
Thereafter either lytic or lysogenic pathway of development takes place depending on the nature of the bacteriophage, state of the bacteria host, nutritive components surrounding the host etc. It is to be noted that Virulent Bacteriophages can follow only lytic pathway, whereas Temperate Bacteriophages can choose between the two pathways.
In the lytic pathway, the bio-synthetic machinery of the host bacteria is hijacked to reproduce viral genome and proteins. This is followed by assembling and packing to form the progeny virions. The late enzymes holin and endolysin are then synthesized to assist in cell lysis and liberation of the virions to the extracellular environment to infect other bacteria.
In the lysogenic pathway, the genome of the bacteriophage integrates into the host bacteria by physical incorporation into the bacterial chromosome in the form of an endogenous prophage. The prophage remains dormant for many host generations until the lytic cycle is induced and is replicated as part of the bacterial chromosome. After induction the prophage starts producing viral proteins and copies of viral genome using the resources and bio-synthetic machinery of the bacteria. This process leads to the formation of progeny virus particles, and after completion of the cycle, these virions are released during host cell lysis.
Temperate Bacteriophages follow lysogenic pathway when the host bacteria offer poor growth conditions, because then the lytic pathway would produce very low number of progeny virions.
