Why Phage Can't be the End of Superbug on its Own?

Abstract

The emergence of ultra-resistant superbug due to the widespread use and even abuse of antibiotics has caused people to start dying from common wound infections. It has become a global consensus to crack the superbug problem as soon as possible. In this battle, a virus called "phage" discovered a century ago has become a research hotspot again because of its characteristic of engulfing bacteria. Especially, the emergence of "phage display" technology has made the targeted evolution of viruses possible, and phage has become a potential weapon against superbug. By reviewing the discovery history of phage, dissecting the relationship between phage and bacteria as well as the molecular mechanism of interaction, this paper found that phage and bacteria are not in a simple parasitic relationship with each other, and that bacteria will evolve various active and passive defense mechanisms against phage infection, while phage will further evolve their responses against the various defense mechanisms of bacteria. In this invasion-defense-counter-defense arms race, phage and bacteria interact with each other and coexist in co-evolution. Phage not only indirectly affects human health by influencing the pathogenicity of bacteria, but also directly affects human health by interacting with human immune cells. The specificity and replication variability of phage, the large number of phage-bacteria, the complexity of phage-bacteria interactions and their unknown evolutionary mechanisms, and the insecurity of phage entry into the human body also contribute to the fact that the efficacy of phagotherapy, which has a century-long history, has always been uncertain and not reliable for large-scale application. Therefore, this study concludes that phage cannot defeat superbug alone, providing a new way of thinking about how humans can finally overcome the superbug problem.