Plectasin, a fungal defensin, targets the bacterial cell wall precursor Lipid II

Tanja Schneider; Thomas Kruse; Reinhard Wimmer; Imke Wiedemann; Vera Sass; Ulrike Pag; Andrea Jansen; Allan K Nielsen; Per H Mygind; Dorotea S Raventós; Søren Neve; Birthe Ravn; Alexandre M J J Bonvin; Leonardo De Maria; Anders S Andersen; Lora K Gammelgaard; Hans-Georg Sahl; Hans-Henrik Kristensen

doi:10.1126/science.1185723

Plectasin, a fungal defensin, targets the bacterial cell wall precursor Lipid II

Science. 2010 May 28;328(5982):1168-72. doi: 10.1126/science.1185723.

Authors

Tanja Schneider¹, Thomas Kruse, Reinhard Wimmer, Imke Wiedemann, Vera Sass, Ulrike Pag, Andrea Jansen, Allan K Nielsen, Per H Mygind, Dorotea S Raventós, Søren Neve, Birthe Ravn, Alexandre M J J Bonvin, Leonardo De Maria, Anders S Andersen, Lora K Gammelgaard, Hans-Georg Sahl, Hans-Henrik Kristensen

Affiliation

¹ Pharmaceutical Microbiology Section, Institute for Medical Microbiology, Immunology, and Parasitology, University of Bonn, D-53115 Bonn, Germany.

PMID: 20508130
DOI: 10.1126/science.1185723

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology
Ascomycota / chemistry
Bacillus subtilis / drug effects
Bacillus subtilis / growth & development
Bacillus subtilis / metabolism*
Bacillus subtilis / ultrastructure
Binding Sites
Cell Membrane / metabolism
Cell Wall / metabolism*
Computer Simulation
Defensins / metabolism*
Defensins / pharmacology
Fungal Proteins / metabolism*
Fungal Proteins / pharmacology
Models, Molecular
Nuclear Magnetic Resonance, Biomolecular
Oligonucleotide Array Sequence Analysis
Peptides / metabolism*
Peptides / pharmacology
Protein Conformation
Staphylococcus / drug effects
Staphylococcus / growth & development
Staphylococcus / metabolism*
Staphylococcus / ultrastructure
Uridine Diphosphate N-Acetylmuramic Acid / analogs & derivatives*
Uridine Diphosphate N-Acetylmuramic Acid / metabolism
Vancomycin / pharmacology

Substances

Anti-Bacterial Agents
Defensins
Fungal Proteins
Peptides
Uridine Diphosphate N-Acetylmuramic Acid
muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol
plectasin
Vancomycin