Use viruses to subdue bacteria？ Phage returns to antibacterial battlefield

　　Use viruses to subdue bacteria? What a "brain hole" this is! However, several small clinical trials at home and abroad have been successful, suggesting that this may be a new way to explore alternatives to traditional antibiotics.

　　Recently, the phage treatment team led by Professor Zhu Tongyu from Shanghai Public Health Clinical Center affiliated to Fudan University and Shanghai Institute of Phage and Drug Resistance successfully cured the patients with urinary tract infection of "superbug" through clinical trials of treating "superbug" with phage. It seems that bacteriophage, as a kind of virus, is better than antibiotics in dealing with the "super bacteria" infection.

　　Historically, bacterial infection was a nightmare for human beings, and plagues such as the Black Death and cholera claimed hundreds of millions of lives. Due to the lack of effective drugs and knowledge of diseases, common diarrhea and wound infection can be fatal. It was not until the discovery and application of antibiotics that this situation improved.

　　Since A. Fleming discovered penicillin in 1928, the application of broad-spectrum antibiotics has saved countless lives. However, long-term use and even abuse of antibiotics have led to the emergence of super-drug-resistant bacteria. Antibiotic-resistant bacteria cause 700,000 deaths every year. If this phenomenon is not solved, it is estimated that the number of deaths caused by antibiotics will reach 10 million every year in 2050. This number will exceed the total number of people who die of cancer every year, but compared with the upsurge of research and development of anticancer drugs, the investment in research and development of new antibacterial drugs is far from its demand, and mankind has returned to the predicament of no drugs available in the pre-antibiotic era.

　　In nature, antibiotics are the weapons used by fungi to compete with bacteria for resources, but bacteriophage is the number one enemy of bacteria. Phage is a kind of virus that specifically infects bacteria, with a total amount of about 1031, which exceeds the sum of all other organisms and is the decisive force to maintain the number of bacteria in the ecosystem. As early as 1917, before the discovery of penicillin, F. d’Hérelle discovered and named phage, and used its characteristics of infecting and "eating" bacteria to open the prelude of bacteriophage antibacterial therapy in France. Since then, phage therapy was once the best choice to fight bacterial infections, and the targets of phage therapy have also been broadened to bacterial infections such as skin diseases, meningitis and typhus. However, due to the lack of understanding of phage, the effect of phage therapy was mixed, and it was replaced by broad-spectrum bactericidal antibiotics in the 1940s.

　　Today, our understanding of phage is not what it used to be. Phage fungicides are widely used in ready-to-eat food processing and animal aquaculture, and phage therapy has returned to people’s field of vision. Compared with antibiotic therapy, phage has a wide range of sources and species; Each species has evolved the ability to destroy a kind of bacterial host, and does not infect humans and other normal flora in the human body, which is a natural version of precise treatment; Phage can use the host bacteria to proliferate and co-evolve with the host bacteria, so it also has the advantage of being outnumbered and strong. These characteristics of phage are often its shortcomings, and the rich phage library, large-scale production technology and standardized quality control and efficacy standards are urgent problems to be solved in phage therapy.

　　In 2017, it was reported that the patients infected with Acinetobacter baumannii in the pyramids were cured by phage; in 2019, the infection of non-tuberculous mycobacteria in British lung transplant girls was cured by genetically modified phage; and in 2018 and recently, two cases of urinary tract infection of Klebsiella pneumoniae in Shanghai were cured, which made people regain their confidence in phage therapy. We believe that phage therapy will become an important weapon to deal with bacterial drug resistance. (Wu Nannan)