Antibiotic resistance is becoming the biggest threat to global health. At the same time, phage therapy is witnessing a return of interest. The therapeutic use of bacteriophages that infect and kill bacteria is a suitable strategy to combat antibiotic resistance. Furthermore, bacteriophages are increasingly used in combination with standard antibiotics against drug-resistant pathogens. Interestingly, we found that the engineered mycobacteriophage phAE159 and natural phage D29 cannot infect the Mycobacterium tuberculosis in the presence of kanamycin, hygromycin or streptomycin, but the phage infection was not affected in the presence of spectinomycin. Based on a series of studies and structural analysis of the above four aminoglycoside antibiotics, it could be speculated that the amino sugar group of aminoglycoside might selectively inhibit mycobacteriophage DNA replication. Our discovery that broad-spectrum antibiotics inhibit phage infection is of great value. This study will provide guidance for people to combine phage and antibiotics to treat M. tuberculosis.

Antibiotic-resistant bacteria infections pose a threat to public health. Considering the difficulty in developing new antibiotics, it is an urgent need to develop alternative therapies against bacterial pathogens. Bacteriophages (phages) are evaluated as potential substitutes or adjuncts of antibiotics because they are abundant in nature and could specifically lyse bacteria. In this review, we briefly introduce phage therapy and its advantages compared with traditional antibiotic therapy. We also summarize new emerging phage technologies, such as CRISPR-Cas, synthetic phages, etc., and discuss some possible obstacles and potential risks in the application process. We believe that, with the advancement in synthetic biology and delivery technology, phage therapy has broad prospects in the future.

Antibiotic resistance is becoming the biggest current threat to global health. At the same time, phage therapy is witnessing a return of interest. The therapeutic use of bacteriophages, that infect and kill bacteria, is well suited to be a good strategy to combat antibiotic resistance. Furthermore, bacteriophages are increasingly used in combination with standard antibiotics against the drug-resistant pathogens. Interestingly, we found that the engineered mycobacteriophage phAE159 and natural phage D29 can not infect the Mycobacterium tuberculosis in the presence of kanamycin, hygromycin or streptomycin, but there is no effect on the phage infection in the presence of spectinomycin. Based on a series of studies and structural analysis of the above four aminoglycoside antibiotics, we can speculate as to the mechanism by which amino sugar group of aminoglycoside was able to selectively inhibit mycobacteriophage DNA replication. This is a rare discovery that broad-spectrum antibiotics inhibit phage infection. We envisioned that this study will provide guidance for people to combine phage and antibiotics to treat M. tuberculosis .