Antimicrobial peptides: mechanism of action, activity and clinical potential Original paper

What was reviewed?

This paper reviewed the biological origin, structural diversity, mechanisms of action, and clinical potential of antimicrobial peptides (AMPs) as core components of innate immunity and emerging therapeutic agents. The authors synthesized experimental, translational, and early clinical evidence to explain how AMPs act as rapid-response defense molecules against bacteria, viruses, fungi, and parasites, while also shaping immune regulation and tissue homeostasis. The review framed AMPs as multifunctional effectors rather than simple antibiotics, emphasizing their ability to target microbial membranes, intracellular pathways, and host immune signaling simultaneously. It integrated molecular biology, microbiology, immunology, and pharmacological studies to provide a comprehensive account of how AMP structure and physicochemical properties determine biological activity and clinical applicability.

Who was reviewed?

The review drew on studies involving human tissues, immune cells, and epithelial barriers, alongside animal models and in vitro microbial systems. Evidence was synthesized from investigations of AMPs produced by bacteria, plants, invertebrates, and vertebrates, with particular focus on mammalian peptides such as cathelicidins and defensins. Clinical contexts reviewed included patients with bacterial infections, inflammatory diseases, cancer, metabolic disorders, and wound healing impairments, as well as experimental models of sepsis, viral infection, and antibiotic-resistant pathogens. This broad scope allowed the authors to connect AMP biology across species with clinically relevant immune and microbiome-related outcomes.

What were the most important findings?

The review demonstrated that AMPs exert antimicrobial activity through multiple, overlapping mechanisms that reduce the likelihood of resistance development. Cationic AMPs selectively bind negatively charged microbial membranes, leading to membrane disruption, pore formation, or complete lysis, while others penetrate cells to inhibit DNA, RNA, protein synthesis, enzyme activity, or cell wall construction. Major microbial associations highlighted include broad activity against Gram-positive and Gram-negative bacteria, including resistant strains such as Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Importantly for microbiome signatures, the review emphasized that AMPs are not purely microbicidal but also immunomodulatory. Peptides such as LL-37 and defensins regulate cytokine release, chemotaxis, antigen presentation, and the balance between pro-inflammatory and regulatory immune responses. The paper also showed that AMP expression is influenced by microbial metabolites, including short-chain fatty acids, linking commensal microbiota to endogenous AMP production and mucosal homeostasis. However, AMP activity was context dependent, with evidence that dysregulated expression can exacerbate inflammation or promote tumor progression in specific tissues.

What are the greatest implications of this review?

The most important implication for clinicians is that AMPs represent a bridge between antimicrobial defense, immune regulation, and microbiome stability. The findings support AMP-based therapies as potential alternatives or adjuncts to antibiotics, particularly in the context of antimicrobial resistance. At the same time, the review highlights the need for precision in AMP application, as their effects depend on concentration, tissue context, and immune environment. Clinically, this reinforces the concept that supporting endogenous AMP production and preserving microbiome balance may be as important as direct antimicrobial intervention.