Cationic host defence peptides: Innate immune regulatory peptides as a novel approach for treating infections

Abstract

An increase in antibiotic resistance and the emergence of new pathogens has led to an urgent need for alternative approaches to infection management. Immunomodulatory molecules that do not target the pathogen directly, but rather selectively enhance and/or alter host defence mechanisms, are attractive candidates for therapeutic development. Natural cationic host defence peptides represent lead molecules that boost innate immune responses and selectively modulate pathogen-induced inflammatory responses. This review discusses recent evidence exploring the mechanisms of cationic host defence peptides as innate immune regulators, their role in the interface of innate and adaptive immunity, and their potential application as beneficial therapeutics in overcoming infectious diseases.

Expression, purification and characterization of the recombinant cysteine-rich antimicrobial peptide snakin-1 in Pichia pastoris

“…The membrane depolarization activity of recombinant SN-1 was determined using a membrane potential-dependent fluorescent dye, diSC 3 (5). Depolarization of the cytoplasmic membrane by the SN-1 peptides was monitored over a period of 300 sec.…”

“…They are potent and bioactive, and provide a rich source of lead compounds for the discovery of promising novel antibiotics [3]. Due to their low toxicity to eukaryotic cells [4], AMPs can be widely used in the fields of pharmaceutics [3,5], cosmetology [6], veterinary medicine [7], and aquaculture [8], as well as in agricultural and food industries [9]. These peptides exhibit antimicrobial actions on target cells in various ways, such as by perturbation of the microbial cell membrane, or by inhibition of the synthesis of nucleic acids, proteins, enzymes, and cell-wall components that are essential for the survival of microorganisms [10].…”

“…These peptides exhibit antimicrobial actions on target cells in various ways, such as by perturbation of the microbial cell membrane, or by inhibition of the synthesis of nucleic acids, proteins, enzymes, and cell-wall components that are essential for the survival of microorganisms [10]. Whether expressed constitutively in certain tissues or induced in response to pathogens [11,12], most AMPs share several common characteristics: they are small peptides (12-100 amino acids), have a net positive charge (+2 to +9), and are amphipathic and cysteine-rich with a disulfide bond-stabilized structure [5,13].…”

Membrane interactions of designed cationic antimicrobial peptides: The two thresholds

“…Some antimicrobial peptides are also effective against tumor cells [2][3][4][5] and have been proposed to play a role in the regulation of inflammatory responses. 6 Antimicrobial peptides share a limited number of characteristics, including relatively short length (a few tens of residues), net positive charge, 7 and solubility in water or saline. 6 Highly positively-charged antimicrobial peptides, termed cationic antimicrobial peptides (CAPs), exist predominantly as random coil structures in solution, but adopt folded secondary structures in hydrophobic environments, typically with amphipathic helical character wherein charged residues are grouped on one face of the helix, while hydrophobic residues are grouped on the opposite face.…”

“…6 Antimicrobial peptides share a limited number of characteristics, including relatively short length (a few tens of residues), net positive charge, 7 and solubility in water or saline. 6 Highly positively-charged antimicrobial peptides, termed cationic antimicrobial peptides (CAPs), exist predominantly as random coil structures in solution, but adopt folded secondary structures in hydrophobic environments, typically with amphipathic helical character wherein charged residues are grouped on one face of the helix, while hydrophobic residues are grouped on the opposite face. 8 In general, CAPs are active in the low-medium micromolar range and show little target or L-vs. D-residue specificity (enantiomers usually exhibit similar or two-fold higher activity when compared with their L-counterparts), indicating that they interact with achiral components of the cell membrane 9,10 through a mechanism of physical disruption.…”