An update on experimental to large-scale production of bacteriophages against superbugs: a review

The escalating problem of antibiotic resistance has sparked renewed interest in bacteriophages (phages) as potential substitutes for conventional antibiotics in treating infectious diseases, improving food safety, and advancing sustainable agriculture. The key phage research processes, such as host range, burst size, and environmental stability tests, strongly influence phage production processes. Hence, the standardization of the mentioned techniques must be prioritized. The introduction of high-throughput sequencing technologies with high accuracy and the emergence of novel bioinformatic tools to analyze the resulting raw molecular data provide comprehensive identification of phages and phage-verse (the universe of phage). While encapsulation of phages was studied comprehensively before, the production of encapsulated phages is still unclear. Moreover, recent advances in artificial intelligence (AI) contribute to phage research by increasing the accuracy of bioinformatic tools, improving resistance profiling, and facilitating phage host prediction. Incorporating AI promises a future of automated, precisely tailored phage applications. This review covers efficient techniques appropriate for industrial and agricultural applications as well as large-scale phage production methods, covering upstream and downstream processing. Also, encapsulated phage production and AI-based automated systems in various applications are proposed in this review. By covering both present issues and potential future uses of phages in the fight against antibiotic resistance, this review seeks to give academics and industry experts the fundamental information they need to advance phage-based solutions.