Fatal Attraction Evaded: How Pathogenic Bacteria Resist Cationic Polypeptides

Antimicrobial polypeptides are widely distributed effectors of host defense in animals and plants. They include enzymes that digest vital microbial structures (e.g., lysozyme, neutrophil elastase, phospholipase A2), substances that bind and sequester iron or other essential nutrients (e.g., lacto-ferrin), and polypeptides that insert into and disrupt microbial membranes (e.g., bactericidal permeability-inducing protein, defensins, cathelicidins; references 1 and 2). Despite their diverse sizes, structures, and mechanisms of action, nearly all antimicrobial proteins and peptides have a net cationic (positive) charge. It is thought that the electrostatic attraction of cationic polypeptides increases the deposition of the polypeptides onto the negatively charged microbial surfaces and thereby promotes their effectiveness. In support of this model, the activity of most but not all antimicrobial polypeptides is competitively inhibited by increasing the ionic strength of the medium 3,4,5 whose solute...