Bacteriophage therapy is now considered to be the best alternative therapeutics to antibiotic treatment. Although phage therapy was started in 1919, the concept of phage therapy died out in the 1940s due to the production of antibiotics in large amount. Over last few decades, due to the emergence of antibiotic resistance, phage therapy is now thought to be a great solution to the antibiotic crisis. In spite of having a lot of advantages of using phage therapy over antibiotics, phage therapy has also some limitations.
1. Phages can’t kill a wide range of pathogens:
Narrow host range can be a disadvantage as the specific phage might not be able to constantly lyse all the pathogenic strains of that certain infection. There are several options to circumvent this problem: using phage with broad host range, using mutant bacteriophage or using a mixture of different phages.
2. Phages cause adverse biological effects:
An unpurified phage preparation can cause several biological effects during phage therapy. Phage multiplication using host cell is a primary step for phage production. During cell lysis, lipopolysaccharide, a component of the cell wall of gram-negative bacteria are released. Lipopolysaccharide acts as an endotoxin and if they are present in high concentration then they can trigger a coagulation cascade, modify hemodynamics, and invoke fever, toxic shock, and hypotension. Purifying phage preparation using chromatography and ultrafiltration can produce endotoxin-free preparation.
3. Temperate phages aren’t antibacterial:
Not all phages can be used for therapeutic propose. Only obligate lytic phages that lyse the bacterial cell directly instead of integrating its genome in bacterial DNA (temperate) are usable for phage therapy. Temperate phages play a major role in the exchange of genetic material between different bacterial strains and often they contribute to the pathogenicity. Some known examples are Cholera toxin from CTXΦ phage and Shiga toxin from H-19B phage acquired by Vibrio cholerae and E.coli respectively.
4. The emergence of phage resistance:
Development of phage-resistant mutation can make the phage therapy unproductive. However, using phage cocktail (a mixture of phages) that uses different cell receptors can restrain rise of phage resistance.
5. Immune response to inactivate phages:
Phage inactivation by human serum can pose a limitation in phage therapy. Some studies have indicated inactivation of phage by human serum while other experiments have documented little or no inactivation or inactivation after a long period of incubation.