Editors' ChoiceImmunology

Defining Defensins’ Mode of Action

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Science Signaling  01 Jun 2010:
Vol. 3, Issue 124, pp. ec166
DOI: 10.1126/scisignal.3124ec166

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. now show that the fungal defensin plectasin targets cell wall biosynthesis. Biochemical studies identified Lipid II as the cellular target of plectasin, and the residues involved in complex formation were identified using nuclear magnetic resonance (NMR) spectroscopy and computational modeling. Initial studies identified two defensins from invertebrates that also target Lipid II. Plectasin 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.

T. Schneider, T. Kruse, R. Wimmer, I. Wiedemann, V. Sass, U. Pag, A. Jansen, A. K. Nielsen, P. H. Mygind, D. S. Raventós, S. Neve, B. Ravn, A. M. J. J. Bonvin, L. De Maria, A. S. Andersen, L. K. Gammelgaard, H.-G. Sahl, H.-H. Kristensen, Plectasin, a fungal defensin, targets the bacterial cell wall precursor Lipid II. Science 328, 1168–1172 (2010). [Abstract] [Full Text]