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Science 328 (5982): 1168-1172

Copyright © 2010 by the American Association for the Advancement of Science

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

Tanja Schneider,1 Thomas Kruse,2 Reinhard Wimmer,3 Imke Wiedemann,1 Vera Sass,1 Ulrike Pag,1 Andrea Jansen,1 Allan K. Nielsen,4 Per H. Mygind,4 Dorotea S. Raventós,4 Søren Neve,4 Birthe Ravn,4 Alexandre M. J. J. Bonvin,5 Leonardo De Maria,4 Anders S. Andersen,2,4 Lora K. Gammelgaard,4 Hans-Georg Sahl,1 Hans-Henrik Kristensen4,*

Abstract: Host defense peptides such as defensins are components of innate immunity and have retained antibiotic activity throughout evolution. Their activity is thought to be due to amphipathic structures, which enable binding and disruption of microbial cytoplasmic membranes. Contrary to this, we show that plectasin, a fungal defensin, acts by directly binding the bacterial cell-wall precursor Lipid II. A wide range of genetic and biochemical approaches identify cell-wall biosynthesis as the pathway targeted by plectasin. In vitro assays for cell-wall synthesis identified Lipid II as the specific cellular target. Consistently, binding studies confirmed the formation of an equimolar stoichiometric complex between Lipid II and plectasin. Furthermore, key residues in plectasin involved in complex formation were identified using nuclear magnetic resonance spectroscopy and computational modeling.

1 Pharmaceutical Microbiology Section, Institute for Medical Microbiology, Immunology, and Parasitology, University of Bonn, D-53115 Bonn, Germany.
2 Statens Serum Institut, 2300 Copenhagen S, Denmark.
3 Department of Biotechnology, Chemistry, and Environmental Engineering, Aalborg University, DK-9000 Aalborg, Denmark.
4 Novozymes AS, DK-2880 Bagsvaerd, Denmark.
5 Department of Chemistry, Faculty of Science, Utrecht University, 3584 CH Utrecht, Netherlands.

* To whom correspondence should be addressed. E-mail: hahk{at}

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