How most antimicrobial peptides kill bacteria—they punch holes in or dissolve bacterial cell membranes.Membrane disruption is the primary bactericidal mechanism of most antimicrobial peptides (AMPs). Cationic AMPs are electrostatically attracted to negatively charged bacterial membranes (phosphatidylglycerol, lipopolysaccharide), then insert and disrupt membrane integrity through several models: barrel-stave (transmembrane pores), toroidal pore (lipid-peptide pores), or carpet model (surface dissolution). This mechanism is difficult for bacteria to develop resistance against because it targets fundamental membrane composition rather than specific protein targets.
