Synergism of phages and antimicrobial peptides for treating multidrug resistant bacterial pathogens

The escalating threat of antibiotic resistance and its advancing mechanisms for resistance development underscore the imperative need for alternative approaches to treat life-threatening infections. Consideration of bacteriophages, as well as antimicrobial peptides (AMPs) that can specifically target and eliminate particular bacteria, is gaining prominence for the improved treatment of infections. The effectiveness of bacteriophages and AMPs has been known for a long time, and their combined use is being investigated recently. Studies have shown that the use of phages or phage-derived enzymes (endolysins) in combination with AMPs has shown promising results in combating multidrug resistant bacteria. Bacteriophages lyse bacteria by hijacking the bacterial cell’s metabolic machinery, leading to the production of phage virus inside it and finally bursting the bacteria, while AMPs act by disrupting the bacterial cell membrane or affecting intracellular targets after penetration. In this review, we discuss previous studies on the combined use of both phages or phage-derived enzymes and AMPs, demonstrating their synergistic effects for combating multidrug resistant pathogens. Their mechanisms of action, and possible mechanisms of synergy and development of bacterial resistance to these, are discussed. Approaches, including genetic engineering, for improving their efficacy have been discussed. Safety and ethical issues regarding their use in human subjects are discussed. In summary, this review emphasizes the need for further research on the combined use of AMPs and bacteriophages to tap their potential effectiveness for treating antimicrobial-resistant infections.