Benefits and Constraints of Bacteriophage Therapy
Bacteriophages are natural antibacterials, and thus offer various superiority compared to Antibiotics. However, they are not still the “magic bullet” to treat any type of infection.
Bacterial Host Specificity
Bacteriophage Therapy has a very narrow antibacterial spectrum with its effect limited to just a single species of bacteria or in some cases a single strain within a species. As a result it does not damage health-protecting normal flora bacteria, or interfere with mammalian cells. Bacteriophages also penetrate deeper as long as the infection is present, and stop reproducing once target bacteria are destroyed.
By contrast, most antibiotics have broader spectra of activity, and thus frequently trigger secondary infection caused by an opportunistic pathogen. Also, antibiotics continue to act even after the infection is cured until excretion and/or degradation.
The high specificity of bacteriophage therapy is a liability too. To define a specific bacteriophage solution, the clinical sample needs to be isolated and cultured for identifying the pathogen. This is a time-consuming process in resource-limited healthcare setup.
This situation can be overcome by using Bacteriophage Cocktails by mixing a selection of potent bacteriophages, resulting in a broader spectrum of activity. Such cocktails are also useful in treating infections caused by genetically different strains of bacteria.
Notwithstanding, a large collection of well-characterized Bacteriophages for a broad range of pathogens are being developed continually, and also methods are being refined to rapidly determine the type of bacteriophage strains effective for any given infection. It is also necessary to sequence the gene of each type of Bacteriophage, as some of these genes might have the potential to promote deleterious side effects.
Nevertheless, the therapeutic use of Bacteriophages is likely to lag behind as new pathogenic bacteria evolve.
Large size of bacteriophage limits its Therapeutic use
The large size of Bacteriophage, along with the inability to prepare highly concentrated solution means that the number of Bacteriophages per dosage is much smaller compared to antibiotics #1. Moreover, the large size of bacteriophage is also responsible for its slow diffusion. So, bacteriophage needs to be applied at the very site of infection where the concentration of bacteria is highest.
Regardless, it is worth mentioning that virulent Bacteriophages rapidly increase in number through replication and thereby self-optimize the dosage, although, these depend on relatively high bacterial densities. Bacteriophage therapy is therefore most useful in treating acute infections.
Bacteriophage Therapy is limited to Virulent Bacteriophages
Virulent Bacteriophages are useful for therapeutic use because these in most cases lyse any bacteria within the hour. The rate of adsorption on the bacterial surface, latent period and burst size of the bacteriophage contribute towards its efficacy #2.
By contrast, bacteriophages following lysogenic pathway are not suitable to treat acute infections due to the delayed induction of the lytic cycle. Moreover, this kind of Bacteriophages can potentially transduce antibiotic resistance genes, leading to the formation of a new microbe or even more resistant bacteria, and also encode bacterial virulence factors, including bacterial toxins.
Despite such benefits, the fact that Virulent Bacteriophages induce the lysis of bacteria, liberating endotoxin and inflammatory mediator, may account for several side effects on the host. For this reason, lysis-deficient bacteriophages and engineered phagemids, that kills the target bacterial cell but is incapable of host cell lysis, are being considered as the better alternatives.
#1: Bacteriophage solution becomes too viscous at higher concentrations.
#2: Latent Period is the time required for host cell lysis after introduction of bacteriophages genome. Burst Size is the number of viral progeny produced per infected bacterium.
