Immunological Response
Since they are viruses, bacteriophages can trigger immunological response, and therefore eliminated from the systemic circulation by reticulo-endothelial system clearance, or inactivated by the adaptive immune defense mechanisms, causing reduced efficacy. However, such immunological response depends on the location of the infection and the way in which bacteriophages are added.
Since, bacteriophages are naturally present in what we eat and drink, its consumption has not led to any immunological complications. However, bloodstream and other internal organs are not their natural environments, and thus intravenous administration of bacteriophages has been shown to activate both the innate and the adaptive immune system. Nevertheless, all bacteriophages are different, and it is thus necessary to test the immunological response of each single bacteriophages.
Bacteriophage Resistance
Bacterial host also develops resistance to a bacteriophage, just as to an antibiotic, resulting in decreased efficacy of bacteriophages. However, compared with antibiotics, bacteriophages exhibit a much narrower potential for inducing resistance because of their high bacterial host specificity.
Various mechanisms may be involved in the process of developing resistance.
- The bacterial host can undergo single point mutation resulting in change of bacterial surface, causing loss or lack of receptor. It may also mask the receptor through secretion of various molecules, such as exopolysaccharide or glycoconjugates. Both these processes prevent adsorption of a specific bacteriophage to the bacteria and generation of new virions. Bacteriophages can counter this through the selection of a new receptor or secretion of exopolysaccharide degrading enzyme.
- The bacterial host may use Superinfection Exclusion (Sie) system to prevent integration of bacteriophage genome.
- The bacteria may also employ Restriction-Modification Defense System or Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) to degrade foreign genome.
- Blocking of bacteriophage replication, transcription, translation, or virions assembly can also be done through the use of Abortive Infection (abi) systems that cause cell death of infected cells before any progeny virions are released.
- Natural selection, temperate phage acquisition and horizontal transmission of plasmid-borne resistance genes will lead to spreading of bacteriophage resistance.
Notwithstanding, new bacteriophages evolve continuously under evolutionary selection to overcome the new resistance. Thus, unlike antibiotics, a few bacteriophages will always have the ability to infect bacteria with resistance to the majority of bacteriophages.
