Human Antimicrobial Peptides: Spectrum, Mode of Action and Resistance Mechanisms

Abstract

Overuse of antibiotics is one of the important factors that contribute to developing antimicrobial resistance. Many studies have been conducted to find out promising solutions to overcome the problems. Antimicrobial peptides (AMPs) are fundamental components of human innate immunity. They have an important role in the treatment of a wide range of diseases, including cancer, allergies, and also in warding off invading pathogens. In the case of infectious disease, the AMPs exhibit broad-spectrum activity against a wide range of pathogens including Gram-positive and -negative bacteria, yeasts, fungi, and enveloped viruses. These peptides have been isolated from various sources such as microorganisms, plants, invertebrates, and vertebrates. The peptides show distinct physicochemical and structural properties but most of them are small cationic peptides with amphipathic properties. In this review, an overview of the classification, antimicrobial activities, mode of action, and mechanism of resistance of human AMPs will be provided. These peptides are categorized into three main groups. The defensins are cationic peptides containing six cysteine residues with three intramolecular disulfide bridges. In humans, two classes of defensins could be found, α-defensins and β-defensins. The second group is cathelicidins that only one AMP, LL-37, has been found in humans. This peptide is derived from proteolytic digestion of the C-terminal of human CAP18 protein. The third group is the family of histatins that are small cationic histidine-rich peptides, and mainly present in human saliva. The last two groups have random coil conformation in hydrophilic environments and α-helices in a hydrophobic environment.