Inevitable triangle interaction in phage therapy: phages – bacteria – immune system

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Phage therapy has been in the spotlight in the last decade as it offers a promising solution to escape from the complex problem of antibiotic resistance. Since its rediscovery, several infection cases have been successfully solved using phage therapy and a number of clinical trials are in progress [1]. Many are in the form of cocktail forms and still combined with minimum antibiotic treatments. Moreover, recently the US FDA has approved the first clinical trial for intravenous phage therapy initiated by University of California San Diego School of Medicine (CA, USA) in collaboration with AmpliPhi Biosciences Corporation (VA, USA) [2]. In this regard, the interaction of each component: bacteria, phages, and the human immune system has been very important. How these three components each play a role in phage therapy?

Red Queen’s race between phages and bacteria

Relationship between phages and bacteria has been explored comprehensively by scientists. It becomes an interesting subject as their interaction is dynamics and keeps evolving. “It takes all the running you can do to keep in the same place” is phrase referred to as the ‘Red Queen’s race’, which is often used to portray an endless co-evolutionary interaction between two organisms, and presumably fits to describe phage–bacteria interaction [3].

Phages have many strategies to infect bacteria at each infection step. Notably, phages can change or modify their tail structure to escape receptor blocking in bacteria during the attachment step. Likewise, during genome replication process, phages can modify their genome to decoy nucleic acid cutting system in bacteria. In fact, some phages can also produce anti-CRISPR protein [4]. On the other hand, bacteria also generate miscellaneous defense mechanisms against phages, noteworthy ones include phase variation, restriction-modification systems and the CRISPR–Cas system [5].

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