The Post-Antibiotic Era: A New Dawn for Bacteriophages

SIMPLE SUMMARY: Phages, also known as bacteriophages, are bacteria-specific viruses that are ushering in a new dawn following the increase in antibiotic resistance. In nature, phages are distributed wherever bacteria exist. They are divided into lytic and lysogenic phages based on their reproduction. Specifically, lysogenic phages reproduce within the bacteria as genetic elements, while lytic phages directly lyse bacteria to release progeny phages. Therefore, lytic phages can be used to treat bacterial infections. However, because the current phage therapy (PT) system has not yet been streamlined, there are still a series of PT-related concerns, such as phage isolation and purification efficiency, the immune response induced by PT, and the impact on intestinal microorganisms. Therefore, synthetic biology, bioinformatics, and artificial intelligence should be combined to edit high-efficiency directionally engineered phages that are safe for humans while effectively killing drug-resistant bacteria. ABSTRACT: Phages are the most biologically diverse entities in the biosphere, infecting specific bacteria. Lytic phages quickly kill bacteria, while lysogenic phages integrate their genomes into bacteria and reproduce within the bacteria, participating in the evolution of natural populations. Thus, lytic phages are used to treat bacterial infections. However, due to the huge virus invasion, bacteria have also evolved a special immune mechanism (CRISPR-Cas systems, discovered in 1987). Therefore, it is necessary to develop phage cocktails and synthetic biology methods to infect bacteria, especially against multidrug-resistant bacteria infections, which are a major global threat. This review outlines the discovery and classification of phages and the associated achievements in the past century. The main applications of phages, including synthetic biology and PT, are also discussed, in addition to the effects of PT on immunity, intestinal microbes, and potential safety concerns. In the future, combining bioinformatics, synthetic biology, and classic phage research will be the way to deepen our understanding of phages. Overall, whether phages are an important element of the ecosystem or a carrier that mediates synthetic biology, they will greatly promote the progress of human society.