Viruses versus bacteria-novel approaches to phage therapy as a tool against multidrug-resistant pathogens

Bacteriophage therapy (the application of phages to treat bacterial infections) has a tradition dating back almost a century, but interest in phage therapy slowed down in the West when antibiotics were discovered. With the emerging threat of infections caused by multidrug-resistant bacteria and scarce prospects of newly introduced antibiotics in the future, phages are currently being reconsidered as alternative therapeutics. Conventional phage therapy uses lytic bacteriophages for treatment and recent human clinical trials have revealed encouraging results. In addition, several other modern approaches to phages as therapeutics have been made in vitro and in animal models. Dual therapy with phages and antibiotics has resulted in significant reductions in the number of bacterial pathogens. Bioengineered phages have overcome many of the problems of conventional phage therapy, enabled targeted drug delivery or reversed the resistance of drug-resistant bacteria. The use of enzymes derived from phages, such as endolysin, as therapeutic agents has been efficient in the elimination of Gram-positive pathogens. This review presents novel strategies for phage-related therapies and describes our current knowledge of natural bacteriophages within the human microbiome. Our aim is to provide an overview of the high number of different methodological concepts, thereby encouraging further research on this topic, with the ultimate goal of using phages as therapeutic or preventative medicines in daily clinical practice.