Bacteriophage Therapy as A Next-Generation Strategy to Combat Antimicrobial Resistance: Recent Advances and Future Perspectives

Abstract

Antimicrobial resistance (AMR) is one of the greatest public health problems in the world today and has become a major cause of concern due to its impact on the effectiveness of currently used antimicrobials and the burden of infectious diseases. Multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant bacterial pathogens are rapidly emerging and spreading and there is an urgent need for alternative therapeutic strategies to combat them. Bacteriophage therapy is one of the most promising strategies, with the possibility of becoming a new generation of a solution against resistant bacterial infection. Bacteriophages, also known as phages, are viruses that infect and lyse bacterial cells, providing a specific and effective way of controlling bacteria. Phages show high host specificity, do not cause changes in beneficial microbiota and can disrupt bacterial biofilms without harming the phages. Molecular biology, genomics, synthetic biology and bioengineering have greatly improved the therapeutic utility of phages in recent years. Thanks to the development of Phage cocktails, genetically engineered Phages, Phage-derived enzymes and Phage-Antibiotic Combination therapies, the range of clinically relevant pathogens to which they are effective has increased to include members of the ESKAPE group. In addition, progress in genome sequencing and bioinformatics has created a speedy identification and characterization of new potential therapeutic phages. In the case of infections that are refractory or resistant to standard drug treatments, clinical trials and compassionate use cases have shown promising results. Although these are all positive steps, there are a number of challenges that remain in the way of clinical implementation of phage therapy. These include the poor specificity of phages, possible phage resistance, regulatory concerns, manufacturing standardisation concerns and lack of large-scale clinical trials. However, novel technologies like the use of engineered phages, artificial intelligence-driven phage discovery and personalized phage therapy are anticipated to overcome many of these. The review provides a summary of the recent progress, therapeutic applications, challenges and future perspectives on the use of bacteriophages as a sustainable and effective approach in combating the escalating global problem of antimicrobial resistance.

Keywords: Antimicrobial Resistance, Bacteriophage Therapy, Enzymes, Genomics, Regulatory Concerns, Artificial Intelligence-Driven