Plectasin, a Fungal Defensin, Targets the Bacterial Cell Wall Precursor Lipid II

Defining Defensins' Mode of Action Defensins are antimicrobial host defense peptides that play a role in innate immunity. Many such peptides act by disrupting the bacterial membrane; however, Schneider et al. (p. 1168 ) now show that the fungal defensin, plecstasin, targets cell wall biosynthesis. Biochemical studies identified Lipid II as the cellular target of plecstasin and the residues involved in complex formation were identified using NMR spectroscopy and computational modeling. Initial studies identified two defensins from invertebrates that also target Lipid II. Plecstasin is active against some drug-resistant Gram-positive bacteria, and its action against a validated target makes it a promising lead for further drug development.