The influencing factors, challenges, optimization strategies and food applications of antimicrobial peptides

The incidence and mortality caused by bacterial infections have increased significantly in the global context of declining efficacy of traditional antimicrobial drugs, placing considerable economic and social burdens on healthcare systems and the food safety sector. However, conventional antibiotics have several limitations, including the promotion of antimicrobial resistance, relatively narrow antimicrobial spectra, and limited efficacy against complex biofilms. Therefore, the development of novel antimicrobial agents has become a major research priority for the global scientific and medical communities. Antimicrobial peptides (AMPs), as the class of naturally occurring or artificially synthesized bioactive molecules, have attracted increasing attention as promising antimicrobial agents. AMPs combine the advantages of natural defense mechanisms with engineered design and exhibit multiple biological activities, including broad-spectrum antimicrobial activity, biofilm clearance capability, host immune modulation, and low resistance potential. Hence, AMPs have emerged as promising alternatives to conventional antibiotics. This review first systematically summarizes the main structural types, physicochemical influencing factors, and action mechanisms of AMPs. This article introduces the challenges faced by AMPs, incliding the differences in their activities, bacterial resistance, and cytotoxicity. Subsequently, this paper focuses on three major aspects (the structural design of AMPs, optimization of delivery systems, and combined application) to deeply analyze the optimization strategies for addressing the challenges of AMPs. Finally, this review discusses the key applications and regulatory status of AMPs in the food industry. This review aims to provide a valuable theoretical and practical reference for the rational design, functional optimization, and broader application of AMPs.