The development of resistance to multiple antimicrobial agents in several important bacterial pathogens has leaded to the search for new antimicrobial agent with novel bacterial targets Antimicrobial peptides (AMPs) are small molecular weight proteins fewer than 100 amino acids residues, cationic and amphipathic. AMPs have been isolated from many organisms such as bacteria, fungi, plants, insects, and animals as well as in human. They have been grouped based on their primary structure, amino acid residue and their size. The therapeutic potential of AMPs are attributed on their membrane lytic properties. The peptides have demonstrated their ability to kill rapidly a broad spectrum of microorganisms including multidrug resistant bacteria, fungi, protozoa and viruses.
Source of AMPs
AMPs have been isolated from many organisms such as bacteria, fungi, plants, insects, and animals as well as in human. They have been grouped based on their primary structure, amino acid residue and their size.
AMPs from insects
More than 150 AMPs peptides have been identified in various insects such as cecropins are one kind AMPs that can be found in insects with 3, 4 kDa linear amphipathic peptides and demonstrate activity against protozoa, metazoan parasites, bacteria and fungi. Fruit fly or Drosophila melanogaster has served drosophila, these peptide can stimulate immune mechanisms. Septic injury in insect rapidly induces the AMP genes in the fat body cells to produce a lineage of peptides namely drosomycin, cecropins, diptericin, drosocin, attacin and metchnikowin. Drosomycin and metchnikowin are strongly antifungi while others show antibacterial properties. Insect defensins have been various found in many species of insect such as from cell cultures of the flesh, Sarcophaga peregrine and from challenged larvae of the black brown fly (Phormia terranovea). Defensins mostly consists of 34-46 residues. All of them share a consensus motif of six cysteines which from intramolecular disulfide bonds. 25-residue AMP of androctonin from the scorpion (Androctonus australis) give highly cationic peptide has four cysteine residues involved in the formation of two intramolecular disulfide bridges. The peptide is active against gram positive and gram negative bacteria and fungi. .
Table 1. A comprehensive list of antimicrobial peptides from insects
AMPs from animal and human
Human defensins can be found in granulocytes, lymphocytes and in intestinal paneth cells. β-defensins also found in humans are of four types viz. human β-defensins (HBD 1-4). These peptides are composed of up to 45 residues and are expressed by the epithelial cells of skin and psoriatic scales. It has been noted that the synthesis of theses peptides can be induced by cytokines.
Cathelicidins possess a 15-18 kDa precursor that contains a highly conserved domain called cathelin. Initially isolated from pig leucocytes, these peptides are stored as inactive propeptides in the secretory granules of neutrophils and are released upon cellular stimulation by proteolytic processing. In human, cathelicidins CAP-18 and LL-37 have been identified in testis, squamous epithelia and different lymphocyte/monocyte population.
Protegrins are isolated from swine neutrophils with 2 kDa peptides composed of 16-18 amino acids. These membrane-disrupting peptides retain activity even in the presence of physiological concentrations of sodium chloride.
Mode of action
The antibacterial or self defence peptides which are usually highly basic, recognize the acidic phospholipids exposed on the surface of the bacterial membrane. In the case of microbes, the anionic lipids are present on the outer surface of the membrane whereas for mammalian cells, anionic lipids are present along the cytoplasmic side of the membrane. This feature might account for their preferential activity against bacteria but not against mammalian cells. One of the major differences between bacterial and eukaryotic cell membranes is the presence of a large amount of cholesterol in eukaryotic cell membranes and a complete absence in bacterial cell membranes. Cholesterol has been shown to protect animal erythrocytes from attack by AMPs. Cholesterol reduces AMP binding and suppresses the disruption of lipid bilayer structure by AMPS.
Figure 1. Molecular basis of cell selectivity of AMPs
Table 2. Antimicrobial peptides demonstrating activity against fungi
Antimicrobial peptides on immunity
In addition to killing bacteria directly they have been demonstrated to have a number of immunomodulatory functions including the ability to alter host gene expression, act as chemokines and/or induce chemokine production, inhibiting lipopolysaccharide induced pro-inflammatory cytokine production, promoting wound healing, and modulating the responses of dendritic cells and cells of the adaptive immune response. Animal models indicate that host defence peptides are crucial for both prevention and clearance of infection.