Bridging phage production models and practical applications to control antibiotic-resistant bacteria.

The emergence of multidrug-resistant (MDR) bacteria represents a significant global health threat, demanding urgent development of alternative treatment strategies. Bacteriophages (phages) have gained attention as promising alternatives to antibiotics due to their specificity, abundance, and minimal side effects, leading to potential applications in food safety, agriculture, aquaculture, and clinical settings. However, the practical use of phage therapy is limited by challenges in efficiently producing phages, due to the complex and dynamic interactions between bacteria and phages. Therefore, this review aims to bridge the gap between theoretical models and practical applications by examining bacteria-phage interactions, focusing on the coevolution of bacteria and phages, their resistance mechanisms, and the environmental factors that influence these interactions. Differential and stochastic mathematical models were used to analyze essential kinetic parameters in phage production and to assess strategies for optimizing phage production and their application in controlling antibiotic-resistant infections. Additionally, mathematical modeling in phage-bacteria dynamics was provided, highlighting new kinetic models that incorporated the evolutionary trade-offs between antibiotic resistance and phage resistance. These models provide valuable insights into the factors that influence bacteria-phage interactions and assist in designing effective treatment strategies to optimize the clinical use of phages by predicting phage behavior and therapeutic effects. Therefore, mathematical modeling serves as an invaluable tool in advancing phage therapy. Further study is needed to increase phage production and improve therapy consistency for establishing phage therapy as a reliable solution for multidrug-resistant infections.