Phage therapy is the use of phage viruses (bacteriophage) to kill bacterial pathogens as well as drug-resistant bacteria that cause life-threatening infection in the human body. Phage therapy was started in 1919, a few years after the discovery of phage by Frederick Twort (1915) and Felix d’He’relle (1917). But a decade later, due to the discovery of first antibiotic penicillin and emergence of pharmaceutical antibiotics in large quantities, the concept of phage therapy died out by 1940s in west Europe. The reluctance of development of phage therapy was also due to the unreliable and inconsistent trial of phage therapy, poor quality control and poor understanding of phage therapy concept. Recent studies say that if the scientists at that time had tried to overcome these problems, phage therapy could have been most effective therapeutics against bacterial pathogens. Moreover, due to the emergence of antibiotic resistance over the past decades and several advantages of phages, phage therapy has drawn a great attention to scientists to combat antibiotic resistance crisis.
- Phage therapy as antibacterial:
Bacteriophages are the viruses that kill virus being the best alternative therapeutics antibiotics. Whereas some antibiotics such as chloramphenicol and tetracycline are bacteriostatic, i.e., those antibiotics do not kill the bacterial cell, which allows bacterial organism become resistant to those antibiotics.
- No adverse effect to the normal host cells:
Replication of phages occurs only at the site of infection thus causing no harm to the normal host cells. Therefore, phage therapy is safe or have a less side effect compared to those of antibiotic treatment.
- Phages don’t disrupt the beneficial bacteria:
The ability of the phage to infect only a few strains of a specific bacterial species or rarely infecting closely related bacterial genus is an advantageous feature since they most likely will not affect the normal flora bacteria. On the other hand, treatment involving broad-spectrum antibiotics not only disrupt the beneficial bacteria but also often lead to superinfection e.g., antibiotic-associated Candida albicans yeast infections and Clostridium difficile colitis.
- Phages in decreasing bacterial pathogenicity:
Often in the process of acquiring phage resistance, bacterial organism lose their virulence when bacterial cell removes their phage receptors from the surface which are an important component in their pathogenicity.
- Bacteria can’t be resistant to phage:
Since the mechanism of bacterial cell lysis by phage is different from that of the chemical antibiotic, the evolution of antibiotic resistance doesn’t correlate with the phage resistance. Therefore, phages can be used to treat infections caused by antibiotic-resistant strain such as multi-drug resistant Staphylococcus aureus. If the resistance of bacteria to phages occurs then phages do evolve themselves naturally to enable their killing ability in infecting the resistant bacteria as the frequency of mutation in phage is significantly higher than that of bacteria.
- Phages cause inhibition of biofilm formation:
Biofilms- multicellular complex of bacteria- cause a disease more potent than a single bacteria does. It was observed that Biofilms are significantly more resistant to chemical antibiotics than planktonic bacterial cells. However, in some cases, phages were documented to have the ability to clear biofilms. Some phages have the ability to produce exopolymer-degrading depolymerase which helps them degrade the outer surface of the cell and easily access the cell membrane to infect and replicate.
- Phages enhance the efficacy of antibiotics:
Bacteriophages can be versatile in formulation development and application form. They can be administrated along with antibiotics, which was found to be more effective in some instance than any single treatment. Phages can be applied in different forms, such as cream, liquid, impregnated in solid etc. Additionally, phages are suitable for the most route of administration. Different phages with different host specificity can be mixed to widen their range of antibacterial activity for the formulation
- No adverse effect to the environment:
Because phages will not infect all the bacterial species due to their specific host range, discarded therapeutic phage will have a less environmental impact, unlike broad-spectrum antibiotics which will interact with all the organism it comes in contacts with. Moreover, phages are susceptible to various environmental factors such as high temperature, desiccation or sunlight which can quickly inactivate them.
- Cost of phage production is relatively low:
The phage production involves multiplication of phage in host bacterium by culturing and subsequent purification. Depending on the host bacterium, the cost of host growth varies but as the technology advances the cost of phage purification is expected to be going down.
- Easy development of phage therapy:
As phages are abundant in the environment and highly specific to the specific strain of bacteria, it is easy to develop new phage treatment quickly. On the other hand, the development of new chemical antibiotics is getting difficult due to the rapid emergence of antibiotic resistance.