Antimicrobial peptides as promising antibiotic adjuvants to combat drug-resistant pathogens

The widespread antimicrobial resistance (AMR) calls for the development of new antimicrobial strategies. Antibiotic adjuvant rescues antibiotic activity and increases the life span of the antibiotics, representing a more productive, timely, and cost-effective strategy in fighting drug-resistant pathogens. Antimicrobial peptides (AMPs) from synthetic and natural sources are considered new-generation antibacterial agents. Besides their direct antimicrobial activity, growing evidence shows that some AMPs effectively enhance the activity of conventional antibiotics. The combinations of AMPs and antibiotics display an improved therapeutic effect on antibiotic-resistant bacterial infections and minimize the emergence of resistance. In this review, we discuss the value of AMPs in the age of resistance, including modes of action, limiting evolutionary resistance, and their designing strategies. We summarise the recent advances in combining AMPs and antibiotics against antibiotic-resistant pathogens, as well as their synergistic mechanisms. Lastly, we highlight the challenges and opportunities associated with the use of AMPs as potential antibiotic adjuvants. This will shed new light on the deployment of synergistic combinations to address the AMR crisis.