Examining alternative approaches to antibiotic utilisation: A critical evaluation of phage therapy and antimicrobial peptides combination as potential alternatives

Abstract

Antimicrobial peptides (AMPs) and bacteriophages, though long recognised, have gained significant attention in recent antimicrobial research due to the rapid evolution of microbial resistance to existing antibiotics. This publication comprehensively examines the current literature on the potential of AMPs and bacteriophages to treat infections caused by antimicrobial-resistant bacteria, either as monotherapies, in combination with existing antibiotics, or in synergy with each other. Bacteriophages kill bacteria by injecting their genomes (DNA or RNA), leading to bacterial cell lysis, while AMPs can either disrupt bacterial cell membranes or interfere with their intracellular targets after penetrating the cell, causing cell death. Our review highlights that both AMPs and bacteriophages have been successfully employed in vitro, in clinical trials, and in patient treatments to eliminate bacterial isolates. Notably, studies combining AMPs and bacteriophages, though not yet widespread, have demonstrated remarkable efficacy. For example, one study investigated the combined use of Lys11, an endolysin derived from phage ϕ11, and the AMP R8K against Staphylococcus aureus. The results indicated that pre-treatment with R8K significantly increased the susceptibility of S. aureus to Lys11-mediated lysis, even at low concentrations. While the precise mechanisms underlying the synergistic action of AMPs and bacteriophages remain unclear, our findings underscore the need for further research in this promising domain. Regarding safety, numerous studies affirm the general safety of bacteriophages due to their specificity for bacterial cells. However, concerns about phage evolution potentially eliciting human immune responses necessitate additional investigation to enhance phage therapy. The issue of safety also extends to the recommended purification of AMPs when used in conjunction with bacteriophages to prevent adverse immune reactions in patients. In conclusion, this review advocates for intensified research into the combined use of AMPs and bacteriophages, emphasising their potential to revolutionise the treatment of antimicrobial-resistant infections.