A combination therapy of Phages and Antibiotics: Two is better than one

Emergence of antibiotic resistance presents a major setback to global health, and shortage of antibiotic pipelines has created an urgent need for development of alternative therapeutic strategies. Bacteriophage (phage) therapy is considered as a potential approach for treatment of the increasing number of antibiotic-resistant pathogens. Phage-antibiotic synergy (PAS) refers to sublethal concentrations of certain antibiotics that enhance release of progeny phages from bacterial cells. A combination of phages and antibiotics is a promising strategy to reduce the dose of antibiotics and the development of antibiotic resistance during treatment. In this review, we highlight the state-of-the-art advancements of PAS studies, including the analysis of bacterial-killing enhancement, bacterial resistance reduction, and anti-biofilm effect, at both in vitro and in vivo levels. A comprehensive review of the genetic and molecular mechanisms of phage antibiotic synergy is provided, and synthetic biology approaches used to engineer phages, and design novel therapies and diagnostic tools are discussed. In addition, the role of engineered phages in reducing pathogenicity of bacteria is explored.

Automated summary

The emergence of antibiotic resistance is a major challenge for global health, leading to an urgent need for alternative therapeutic strategies due to a shortage of antibiotic pipelines. Phage-antibiotic synergy (PAS) has emerged as a promising approach to combat antibiotic-resistant pathogens, by enhancing bacterial killing and reducing the development of antibiotic resistance through a combination of phages and antibiotics. Additionally, the genetic and molecular mechanisms of phage antibiotic synergy, as well as the potential of engineered phages in reducing bacterial pathogenicity, are addressed in this review.