The resurgence of phage-based therapy in the era of increasing antibiotic resistance: From research progress to challenges and prospects

Phage therapy was implemented almost a century ago but was subsequently abandoned when antibiotics emerged. However, the rapid emergence of drug-resistant, which has brought to the limelight situation reminiscent of the pre-antibiotic era, coupled with the unavailability of new drugs, has triggered the quest for an alternative therapeutic approach, and this has led to the rebirth of phage-derived therapy. Phages are viruses that infect and replicate in bacterial cells. Phage therapy, especially phage-derived proteins, is being given considerable attention among scientists as an antimicrobial agent. They are used alone or in combination with other biomaterials for improved biological activity. Over the years, much has been learned about the genetics and diversity of bacteriophages. Phage cocktails are currently being exploited for treating several infectious diseases as preliminary studies involving animal models and clinical trials show promising therapeutic efficacy. However, despite its numerous advantages, this approach has several challenges and unaddressed limitations. Addressing these issues requires lots of creativity and innovative ideas from interdisciplinary fields. However, with all available indications, phage therapy could hold the solution in this era of increasing antibiotic resistance. This review discussed the potential use of phages and phage-derived proteins in treating drug-resistant bacterial infections. Finally, we highlight the progress, challenges, and knowledge gaps and evaluate key questions requiring prompt attention for the full clinical application of phage therapy. •Antibiotic resistance persists as a critical challenge in public health despite scientific advances.•Phage therapy is a promising alternative treatment for drug-resistant pathogens.•Phages and their products can be combined with other biomaterials and bioengineered for increased therapeutic potential and pharmacokinetics.•Phage-mediated gene delivery can be a novel approach to tackle the increasing drug-resistant issue.•Phage anti-CRISPR proteins could be an efficient therapeutic biomaterial against drug-resistant pathogens.