Expanding horizon of antimicrobial peptides: mechanistic complexity and biomedical potential

Antimicrobial peptides (AMPs) are a heterogeneous group of small, naturally occurring molecules that are an integral part of the innate immunity of nearly all life forms. Their amphiphilic nature, cationic character, and small size distinguish AMPs, which have a wide spectrum antimicrobial activity against bacteria, fungi, parasites, and viruses. Their specific ability to selectively destroy microbial membranes, without harming host cells, makes them promising contenders to treat the growing threat of antimicrobial resistance (AMR), which has undermined the effectiveness of traditional antibiotics. The action mechanisms of AMPs are multifaceted, involving both membrane-disruptive mechanisms, like barrel stave pore formation, toroidal pore induction, and carpet-like membrane degradation, and non-membrane targeting mechanisms, like inhibition of nucleic acid synthesis, protein translation, and cell wall biosynthesis. AMPs are structurally diverse, from α-helices and β-sheets to cyclic and unstructured peptides, and are distributed abundantly in nature, being derived from mammals, amphibians, insects, plants, and microorganisms. Apart from antimicrobial activity, AMPs have immunomodulatory and regenerative activities, enabling their use in many therapeutic and industrial applications. These are for the construction of new anti-infective agents, wound healing compounds, medical device coatings to inhibit biofilm growth, natural food preservatives, adjuvants for vaccines, and possible anti-cancer drugs. Although they hold great promise, stability, toxicity, and production scale issues continue to hinder translation to the clinic. This review highlights the structural variability, modes of action, and novel uses of AMPs, with a focus on their status as next-generation therapeutics against multidrug-resistant microbes and for promoting biomedical innovation.