Antimicrobial Peptides and Antibiotics Exert Antibacterial Effects Through a Synergistic Mechanism by Activating Immune Cells: A Review

ABSTRACT The escalating threat of antibiotic resistance has emerged as a formidable challenge to global public health, creating an urgent imperative for the development of novel antimicrobial strategies. As crucial elements of the host's innate immune system, Antimicrobial Peptides (AMPs) are viewed as a compelling alternative or synergistic adjunct to conventional antibiotics, owing to their broad‐spectrum antimicrobial activity, unique bactericidal mechanisms, and low propensity for inducing resistance. Recent studies have revealed that the combined use of AMPs and antibiotics can yield a potent synergistic antimicrobial effect. This approach not only effectively eradicates multidrug‐resistant pathogens but impedes the development of resistance. Significantly, this synergy extends beyond direct microbial killing; it operates by activating and modulating host immune cells, thereby bolstering the host's intrinsic antimicrobial defenses to achieve more thorough and enduring therapeutic outcomes. This review seeks to systematically elucidate the molecular mechanisms underlying synergistic interaction between AMPs and antibiotics, to thoroughly investigate the critical involvement of immune cells in this process, and to assess the existing challenges and prospective future directions in this field of research. The objective is to furnish a theoretical framework and practical guidance for the advancement of innovative anti‐infection strategies founded on combination therapies employing AMPs and antibiotics.