The term bacteriophage or phage is a virus that attacks bacteria. Phages naturally kill bacteria but harmless to human. Based on this fact, in the 1920s, d’Herelle successfully used bacteriophage to treat dysentery infection. This method is termed as Phage Therapy.

As the popularity of antibiotics arises, the research regarding phage therapy become unattractive and unpopular. However, the increasing antibiotic resistance has become worrisome, and thus, the research about phage therapy has once again revisited.

Phage therapy is still unpopular here in Indonesia, but the research about phage therapy has been developing rapidly in the US and Europe countries as one of the alternatives to the resistance problem.

To apply phage therapy in human infection cases, it is pivotal to have a deep understanding of how phages interacting with bacteria can also modify the human immune system. Phages, bacteria, and the human immune system are known to have a complex interaction. Particularly, phages and bacteria, both are known to have arms-race interaction, meaning, alteration in one side can lead to the extinction of the other side. Thus, the only way to survive is by counter‐adaptation.

Phages have their strategy to adapt to the bacterial defense mechanisms, such as changing surface receptors and genome modification. On the other side, bacteria do exactly the same, by evolving and developing novel defense mechanisms, such as CRISPR-Cas.

Undoubtedly, the bacterial population and phage diversity are closely related. To apply phage therapy in human infection cases, it is pivotal to have a deep understanding of how phages interacting with bacteria can also modify the human immune system. Phages naturally present in the human body as a diverse community, therefore naturally interact with the immune response.

Various researches have been looking into phages and innate immune interaction. Generally, phages induce an insignificant immune response. In a context of phage therapy phages could either kill and lysis bacteria so that bacterial particles can activate more immune response. Or, phages can opsonize bacteria and enhances the immune response.

In a clinical setting, phages are proven to cure several deadly infections, which can’t be solved by antibiotics. The recent case of phage therapy clinical application was on a teenage patient with cystic fibrosis who got a lung transplant.

After the transplantation, bacterial infection dispersed on her surgical wound. Despite antibiotics treatment, the Superbug won’t die down. Thus, doctors and scientists propose to use genetically engineered phage to treat the patient.

Over the next six months, nearly all of the patient bruises disappeared, and the surgical wound began to heal. Despite this specific application, the best method on how phages shall be administered generally is still elusive.

Although there are still several blind spots to bring phage therapy to the general application, recently, FDA approved first phage therapy which injected intravenously (IV). A research group from the University of California San Diego (UCSD) School of Medicine which collaborate with AmpliPhi Biosciences Corporation will try phage therapy in phase 1 and two trial. The research will evaluate the efficacy, tolerability, and safety of the therapy for patients with Staphylococcus aureus infections.

Aside from the progressive development of phage therapy, in this paper, we showed ‘the blind spot’ of phage therapy, which needs to be answered. As phage-resistance in bacteria is possible to occur, just like antibiotic resistance, deeper understanding of how phage should be produced to prevent this risk still needs to be elucidated.

Also, we suggest looking deeper in the interaction between phage and T-cells in human, as until this paper published, there is still limited research in this specific area. It can also be a new research area to be explored, especially here in Indonesia, a country which is very rich in microorganism biodiversity, without exception diversity in phages resource.

Author: Rizka Oktarianti Ainun Jariah

Details of this research available at:

Jariah, ROA, Hakim, MS. Interaction of phages, bacteria, and the human immune system: Evolutionary changes in phage therapy. Rev Med Virol. 2019;e2055. https://doi.org/10.1002/rmv.2055