AMPs lipid head groups. However, new research has

AMPs
have a number of different mechanisms of action. It is generally accepted that
the mechanism of action of AMPs can be categorised into two distinct groups,
namely, the ‘disruptive mechanisms’, which is linked with membrane lysis and ‘membrane
non-disruptive mechanisms’, which involves the neutralisation of intracellular
targets.  The disruptive mechanisms are believed to account
for the bactericidal effect of AMPs. The disruptive mechanisms allow the
formation of pores in the bacterial cell membrane, which consequently causes a loss of control
over the flow of ions across the cell membrane. Cell death results. The initial
stage of any mechanism is thought to involve electrostatic interactions between
the positively charged AMP, due to the positive amino acids, and the negatively
charged lipopolysaccharide or phospholipid head of the bacterial cell membrane.
This results in the build-up of AMPs on the surface of the bacterial cell
membrane. When the threshold concentration of AMPs is reached the AMPs encompass
themselves into the bacterial cell membrane creating a pore. The disruptive
mechanisms, that are thought to cause the formation of pores, can be depicted
in three models: the barrel-stave model, the carpet model, and the toroidal
model. In the barrel-stave model the peptides (also referred to as staves) arrange
and position themselves in a manner that allows them to bind to the cell
membranes. This brings about peptide accumulation and transformation to a
bilayer. Subsequently in this manner, the hydrophobic peptides are assembled parallel
with the lipid core and the hydrophilic peptides produce an ‘access pore’ in
the inner portion of the membrane. In the carpet model, the peptides align
themselves parallel to the cell membranes outer surface and form an elongated layer or carpet.
This will ultimately increase the surface tension of the membrane causing
disruption of the membrane. Finally, in the toroidal model the attached
peptides insert perpendicularly into the membrane, consequently, bending the
lipid monolayer continuously through the pores in a way that the core is lined
by the inserted peptides and lipid head groups.  However, new research has suggested that the
interactions between the AMPs and membranes of bacteria could possibly entail many
more specific interactions than those suggested by the three models of pore
formation. E.g. Phosphatidylethanolamine, a class of phospholipid found on the
surface of bacterial cell membranes, has been shown to act as a high affinity lipid receptor for AMPs.
Recent evidence has demonstrated that a wide range of AMPs use receptors, such
as phosphatidylethanolamine, when interacting with membranes. There are many
other specific components of bacterial cell membranes that interact with AMPs
e.g. lipopolysaccharide (LPS), lipoteichoic acid (LTA) and lipid II. The
membrane non-disruptive mechanisms are based on the passage of AMPs across the
bacterial cell membrane, without causing disruption to the membrane, and
inhibiting certain intracellular processes, resulting in cell death. There are
two methods by which AMPs can enter cells. The first method involves
spontaneous translocation across the bacterial cell membrane. The second method
involves the secondary structure of the AMP causing membrane permeabilization.
The ?-helix AMPS and ?-sheet AMPs cause membrane permeabilization in different
ways. The ?-helix AMPs binds to the bacterial cell membrane