Bacteriophages are ancient viruses that exclusively parasitize bacteria. They are extremely diverse in their host range and they target bacteria of all different kinds and sizes. In other words, bacteriophages can be found everywhere, infecting every kind of bacterial species. However, it has long been debated whether bacteria can develop resistance to phage therapy. In this article, we examine the question of whether bugs (bacteria) can develop resistance against phage therapy and, if they can, whether this poses a problem for phage therapy.
Can bacteria develop resistance against bacteriophages?
Yes, bacteria can develop resistance against bacteriophages. It is possible for bacteria to develop resistance to different types of bacteriophages. Unlike antibiotics, bacteriophages can evolve to avoid the resistance mechanisms used by bacteria.
Underlying mechanisms of bacteriophage resistance
There are a number of possible mechanisms by which bacteria can develop resistance against bacteriophages. Bacterial resistance to phage attacks can be achieved through a variety of mechanisms, including spontaneous mutations, restriction-modification systems, and adaptive immunity via the CRISPR-Cas system.
Restriction modification systems
Adaptive immunity via the CRISPR-Cas system
Is Bacteriophage resistance problem to phage therapy?
The quick answer is yes. Although scientists have devised various methods to mitigate this, including the use of phage cocktails, phage training, and even bioengineering the phage particles. Some shocking discoveries have also made the use of phage therapy so intriguing. For example, as bacteria develop resistance to phages, they tend to lose resistance to antibiotics. Mutations in surface virulence factors, such as Lipopolysaccharides (LPS), may cause phage-resistant bacteria to become less virulent. Similarly, the upkeep of anti-viral defense systems, such as DNA restriction-modification enzymes and CRISPR-Cas adaptive immunity, comes at a cost.
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