Bacteriophage therapy beyond antibiotics: emerging innovations for infectious and non-infectious diseases

The advancement of synthetic biology and the rise of antimicrobial resistance have led to the development of bacteriophage therapy for more than antibacterial applications. This review focuses on applications to multidrug-resistant infections, biofilm diseases, cancer research, veterinary medicine and animal production. Recent research suggests phages can be used in combination with antibiotics to enhance treatment of large multidrug resistant pathogens such as Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. This could also help to restore antibiotic sensitivity by making bacteria change resistance related structures or mechanisms. Despite this, there are several challenges for the use of phage therapy prior to its widespread clinical application, including phage resistance, difference in patient response, unknown pharmacokinetic parameters, immune issues, and unclear regulatory guidelines. Additionally, in some cases, phages could also play a role in horizontal gene transfer, raising further safety concerns. Beyond antimicrobial therapy, phage display platforms derived from M13, T7 and λ phages have enabled the identification of tumor-targeting peptides, the development of immunomodulatory constructs, and targeted delivery of therapeutic molecules. Over 100 clinical cases and 44 registered trials support the generally favorable safety profile of personalized phage therapy, and highlight the need for better treatment standardization, controlled clinical evaluation, and better regulatory processes. Additionally, engineered phages expressing biofilm degrading enzymes represent promising tools for disrupting matrix-embedded bacterial communities associated with chronic infections and medical devices. In summary, CRISPR-based engineering and genome refactoring highlight the potential of phage-based therapeutics as complements to conventional antimicrobial therapy, although their broader use depends on overcoming biological, clinical, and regulatory challenges.