Antimicrobial Peptides in Infectious Diseases and Beyond-A Narrative Review

Abstract

Despite recent medical research and clinical practice developments, the development of antimicrobial resistance (AMR) significantly limits therapeutics for infectious diseases. Thus, novel treatments for infectious diseases, especially in this era of increasing AMR, are urgently needed. There is ongoing research on non-classical therapies for infectious diseases utilizing alternative antimicrobial mechanisms to fight pathogens, such as bacteriophages or antimicrobial peptides (AMPs). AMPs are evolutionarily conserved molecules naturally produced by several organisms, such as plants, insects, marine organisms, and mammals, aiming to protect the host by fighting pathogenic microorganisms. There is ongoing research regarding developing AMPs for clinical use in infectious diseases. Moreover, AMPs have several other non-medical applications in the food industry, such as preservatives, animal husbandry, plant protection, and aquaculture. This review focuses on AMPs, their origins, biology, structure, mechanisms of action, non-medical applications, and clinical applications in infectious diseases.

Keywords: antibiotics; antimicrobial peptides; antimicrobial resistance; infectious diseases; microbiology.

Figure 1

The mechanisms of action of AMPs. AMPs may act through the permeabilization of bacterial cytoplasmic membranes in three different ways. In the carpet model, most AMPs are located on the membrane, causing the perturbation of its integrity and the formation of micelles. In the barrel-stave model, the AMPs are inserted into the membrane, causing the formation of a pore with the hydrophilic side facing the interior of the pore and the hydrophobic side towards the lipid core of the membrane. A transmembrane pore model involves the formation of a pore, as in the toroidal-pore model, but the pore is also lined with the hydrophilic side of the AMPs and the head parts of the membrane phospholipids. AMP: antimicrobial peptide.

Figure 2

Graphical representation showing the immunomodulatory function of AMPs. Apart from the direct killing mechanisms of AMPs, they can kill pathogens through the induction of innate and adaptive immunity. AMPs can induce cells involved in innate immunity, such as macrophages (Mφs), polymorphonuclear cells (PMNs), and mast cells. AMP: antimicrobial peptide; DCs: dendritic cells; Mφs: macrophages; PRR: pathogen recognition receptor; PMN: polymorphonuclear cell; ROS: reactive oxygen species; NETs: neutrophil extracellular traps.