Plectasin, a Fungal Defensin, Targets the Bacterial Cell Wall Precursor Lipid II
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- Tanja Schneider
- Pharmaceutical Microbiology Section, Institute for Medical Microbiology, Immunology, and Parasitology, University of Bonn, D-53115 Bonn, Germany.
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- Thomas Kruse
- Statens Serum Institut, 2300 Copenhagen S, Denmark.
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- Reinhard Wimmer
- Department of Biotechnology, Chemistry, and Environmental Engineering, Aalborg University, DK-9000 Aalborg, Denmark.
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- Imke Wiedemann
- Pharmaceutical Microbiology Section, Institute for Medical Microbiology, Immunology, and Parasitology, University of Bonn, D-53115 Bonn, Germany.
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- Vera Sass
- Pharmaceutical Microbiology Section, Institute for Medical Microbiology, Immunology, and Parasitology, University of Bonn, D-53115 Bonn, Germany.
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- Ulrike Pag
- Pharmaceutical Microbiology Section, Institute for Medical Microbiology, Immunology, and Parasitology, University of Bonn, D-53115 Bonn, Germany.
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- Andrea Jansen
- Pharmaceutical Microbiology Section, Institute for Medical Microbiology, Immunology, and Parasitology, University of Bonn, D-53115 Bonn, Germany.
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- Allan K. Nielsen
- Novozymes AS, DK-2880 Bagsvaerd, Denmark.
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- Per H. Mygind
- Novozymes AS, DK-2880 Bagsvaerd, Denmark.
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- Dorotea S. Raventós
- Novozymes AS, DK-2880 Bagsvaerd, Denmark.
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- Søren Neve
- Novozymes AS, DK-2880 Bagsvaerd, Denmark.
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- Birthe Ravn
- Novozymes AS, DK-2880 Bagsvaerd, Denmark.
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- Alexandre M. J. J. Bonvin
- Department of Chemistry, Faculty of Science, Utrecht University, 3584 CH Utrecht, Netherlands.
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- Leonardo De Maria
- Novozymes AS, DK-2880 Bagsvaerd, Denmark.
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- Anders S. Andersen
- Statens Serum Institut, 2300 Copenhagen S, Denmark.
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- Lora K. Gammelgaard
- Novozymes AS, DK-2880 Bagsvaerd, Denmark.
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- Hans-Georg Sahl
- Pharmaceutical Microbiology Section, Institute for Medical Microbiology, Immunology, and Parasitology, University of Bonn, D-53115 Bonn, Germany.
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- Hans-Henrik Kristensen
- Novozymes AS, DK-2880 Bagsvaerd, Denmark.
抄録
<jats:title>Defining Defensins' Mode of Action</jats:title> <jats:p> Defensins are antimicrobial host defense peptides that play a role in innate immunity. Many such peptides act by disrupting the bacterial membrane; however, <jats:bold> Schneider <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="1168" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1185723">1168</jats:related-article> ) 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. </jats:p>
収録刊行物
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- Science
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Science 328 (5982), 1168-1172, 2010-05-28
American Association for the Advancement of Science (AAAS)