Antibacterial peptides are a group of peptides with diverse functions which serve as antimicrobial agents, and have been shown to be produced in a variety of cell types in the host. They are induced by microbes and cytokines as part of the innate immune response.
They have antimicrobial activity against a broad range of Gram-positive and -negative bacteria, fungi, and viruses (reviewed in [1]). Many AMPs have antibacterial MIC values in the 1-50mg/ml range.
The antimicrobial properties of AMPs are governed by a number of factors including the physical characteristics of their amino acid side chains, their ability to interact with the membrane surface, and their binding affinity for the bacterial outer leaflet of the membrane.
Cationic AMPs attach to the outer leaflet of bacterial outer membranes through electrostatic interactions with the negatively charged phosphate groups and anionic lipids that surround them. This cationic interaction forms the basis of the ability of AMPs to kill bacteria.
When AMPs bind to the membrane they adopt an energetically favorable secondary structure regulated by their hydrophobicity, and can take on different membrane orientations ranging from parallel to perpendicular to the membrane. This morphology is dictated by the peptide’s amino acid side chain polarity, and is the reason why a-helical AMPs are generally more effective than b-helical AMPs.
The majority of antimicrobial peptides follow a two-step mechanism of aggregation and attachment to the membrane. They first bind to the surface of the membrane, then insert perpendicularly into the monolayer. During this phase the monolayer is initially stretched and pores form. The peptides then induce a continuous bend in the membrane to create toroidal pores that disrupt the lipid core of the membrane.