Antimicrobial Peptides (AMP)

Antimicrobial peptides (AMPs) are a potential source of antimicrobial agents that could replace antibiotics. AMPs, a broad class of antimicrobial compounds, are found in the immune systems of organisms and are peptides with a high net positive charge and a mixture of hydrophilic and hydrophobic regions along their length, also known as defense peptides against pathogens mansion. It is believed that the high positive charge enables AMPs to accumulate on the surface of a pathogen’s membrane, forming pores and entering the cell.

Approximately 600 antimicrobial cationic peptides can be mentioned, including mellitin, secropin, magainin, nisin, peksiganan (MSI-78), cathelicidin LL-37, defensin, dipterisins, and bombinin such as.

Structural Properties of AMPs

They can be examined in two parts: primary and secondary structure.

Primary Structure

AMPs typically consist of 12 to 50 amino acids and possess a positively charged structure. Their net positive charge is generally +2 but can sometimes reach +4, +6, or +7.

Secondary Structure

These are three-dimensional structures formed either through disulfide bonds within the peptide or by folding upon interaction with the bacteria membrane. The hydrophilic portion of these structures consists of polar positively charged amino acids, while the hydrophobic portion contains nonpolar neutral amino acid side chains. Thanks to this amphipathic structure, AMPs can interact with bacterial membranes that have hydrophobic interiors and negatively charged hydrophilic exteriors.

The secondary structures of antimicrobial cationic peptides can be grouped into four categories.

1. Peanut-shaped peptides
2. Helical peptides
3. Ring-structured peptides
4. Long-chain peptides

Mechanism of Action of AMPs

The primary mechanism of action of cationic AMPs involves electrostatic interaction interaction with the negatively charged bacterial membrane, leading to membrane disruption and release of cellular contents road. This occurs when the hydrophobic region of these amphipathic AMPs binds to the lipid bilayer and the hydrophilic regions interact with phospholipid head groups. Through these interactions, AMPs accumulate on the membrane surface and aggregate to form pores in the cytoplasmic membrane.

Some Hypothetical Models of Pore Formation

Pore formation is explained through the barrel-stave, toroidal pore, and carpet models.

Barrel-Stave Model

In the barrel-stave model, as the number of peptides bound to the membrane increases, local phospholipid groups shift and the membrane thins. Peptide aggregates orient perpendicularly along the hydrophobic region of the lipid bilayer, forming a channel where the hydrophilic portions face inward. The hydrophobic regions interact with membrane lipids, while the hydrophilic regions form the lumen of the pore.

Toroidal Pore Model

The toroidal pore model, similar in mechanism to the barrel-stave model, is based on the principle that peptide spirals bind to lipids to form peptide-lipid complexes rather than peptide-peptide interactions, creating toroidal pore complexes. At high concentrations, locally accumulated AMPs induce bending deformations in lipid molecules, resulting in toroidal pore formation.

Carpet Model

In the carpet model, electrostatic interaction between cationic AMPs and anionic membranes is necessary, but high concentrations of AMPs are required to form micelles and disrupt the microbial membrane none. When the peptide concentration reaches a threshold, AMPs cover the membrane in clusters and cause membrane rupture in a manner similar to surfactants substance. Peptides do not insert into the hydrophobic region of the membrane nor form channels. This effect involves complete or partial disruption of the cell membrane, leading to cell death.