Antimicrobial peptides: mechanism of action, activity and clinical potential

Abstract

The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria. As an excellent candidate to overcome antibiotic resistance, antimicrobial peptides (AMPs) that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity. These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action. This comprehensive review provides a broad overview of AMPs from the origin, structural characteristics, mechanisms of action, biological activities to clinical applications. We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.

Keywords: Antimicrobial peptides; Antimicrobial resistance; Biological activity; Clinical application; Mechanism of action.

Fig. 1

Models of antibacterial mechanisms of AMPs. The direct bactericidal mechanism of AMPs is performed through interacting with negatively charged membranes, resulting in increased membrane permeability, cell membrane lysis, or release of intracellular contents, which ultimately leads to cell death. There are four main models of membrane-pore formation, namely barrel-stave model, toroidal-pore model, carpet model and aggregate model. After AMPs penetrate into the phospholipid membrane, their hydrophobic regions combine with the internal hydrophobic regions of the phospholipid bilayer, while their hydrophilic regions are exposed to the outside. Another bactericidal mechanism is that AMPs penetrate into the cytoplasm and interact with intracellular substances, such as inhibiting DNA, RNA and protein synthesis, inhibiting protein folding, inhibiting enzyme activity and cell wall synthesis, and promoting the release of lyases to destroy cell structures. AMPs antimicrobial peptides

Fig. 2

The immunomodulatory mechanisms of AMPs. AMPs not only directly kill invading pathogenic microorganisms, but also indirectly kill them by activating the immune system. On the one hand, AMPs can activate immune cells such as neutrophils, macrophages, mast cells and NK cells in the innate immune system and induce the production of cytokines and chemokines to engulf pathogenic bacteria and kill them. On the other hand, AMPs are also able to activate adaptive immune responses, present antigens to T cells by activating dendritic cells (DCs), and induce the activation of cytotoxic T cells to kill pathogenic bacteria. AMPs antimicrobial peptides; NK natural killer

Fig. 3

The tumor modulatory mechanisms of AMPs. AMPs play a dual role in promoting or inhibiting the occurrence and development of cancer. AMPs not merely directly affect the process of the occurrence of cancer cells, cell proliferation and metastasis, but also promote or inhibit these capabilities of cancer cells by mediating stromal cells in the immune microenvironment and other tumor microenvironment. AMPs antimicrobial peptides