Engineering therapeutic phages for enhanced antibacterial efficacy

Abstract

The alarming rise in antimicrobial resistance coupled with a lack of innovation in antibiotics has renewed interest in the development of alternative therapies to combat bacterial infections. Despite phage therapy demonstrating success in various individual cases, a comprehensive and unequivocal demonstration of the therapeutic potential of phages remains to be shown. The co-evolution of phages and their bacterial hosts resulted in several inherent limitations for the use of natural phages as therapeutics such as restricted host range, moderate antibacterial efficacy, and frequent emergence of phage-resistance. However, these constraints can be overcome by leveraging recent advances in synthetic biology and genetic engineering to provide phages with additional therapeutic capabilities, improved safety profiles, and adaptable host ranges. Here, we examine different ways phages can be engineered to deliver heterologous therapeutic payloads to enhance their antibacterial efficacy and discuss their versatile applicability to combat bacterial pathogens.