Antibacterial peptides are a key component of host defense against microbial infection and form an important link between innate and adaptive immunity. Their elicitation depends on many different cellular events, including phagosome-lysosome fusion in macrophages and neutrophils, extracellular secretion from confined extracellular spaces such as gingival epithelial cells in the gingival crevice or Paneth cells in the base of the intestinal crypts, and direct secretion by keratinocytes on bacteria bound to the plasma membrane.
Antimicrobial peptides are characterized by their linear structure with a kink or hinge in the middle of the molecule that allows them to adopt an a-helical secondary structure upon interaction with membranes . The majority of AMPs are cationic and display amphipathicity due to the presence of arginine and tryptophan side chains. These characteristics allow AMPs to interact with phospholipids forming a strong electrostatic association which is stabilized by the polar head groups of the lipid membrane.
The physical properties of AMPs also make them susceptible to protease digestion. This effect can be mitigated by the inclusion of disulfide bonds which render AMPs less sensitive to proteases (e.g. LL-37).
The initial interaction of the peptide with bacteria is determined by its amphipathicity, and the distribution of hydrophobic and polar residues on its surface. This enables the peptide to penetrate the outer lipopolysaccharide (LPS) or teichoic acid layers of Gram-negative bacteria or phosphate head groups of Gram-positive LPS and lipid A of the bacterial inner membrane. This interaction is essential for AMP function, but it may not be the final step in the process of antimicrobial activity. AMPs also show non-microbicidal related activities such as chemotactic and immunomodulatory effects and are a potential source of new immune therapeutics.