5月28日,,《科學(xué)》雜志報道稱,某些真菌用一種防御性的肽,,或稱防御素,,來擊退細(xì)菌,這種防御素實際上抑制了細(xì)菌細(xì)胞壁的形成,,而不是像其它的防御素那樣簡單地破壞了細(xì)菌的細(xì)胞膜,。
將來,這一發(fā)現(xiàn)可為抗菌藥物的研發(fā)提供新的而且有效的標(biāo)靶,。 Tanja Schneider及其同僚對一種特別的真菌防御素菌絲霉素(plectasin)做了無數(shù)的遺傳學(xué)和生物化學(xué)研究,,并發(fā)現(xiàn)它可直接與Lipid II(這是細(xì)菌細(xì)胞壁的一個基本成分)結(jié)合。
研究人員還利用了核磁共振(NMR)加上電腦模型來尋找菌絲霉素中的與Lipid II結(jié)合的關(guān)鍵殘基,。 因為菌絲霉素具有抗某些耐藥性格蘭氏陽性細(xì)菌的活性,,而且研究人員過去曾經(jīng)在無脊椎動物中找到另外2種以Lipid II為標(biāo)靶的防御素,因此這一發(fā)現(xiàn)可能會在將來被用于發(fā)現(xiàn)更多有效的抗菌藥物,。(生物谷Bioon.com)
生物谷推薦原文出處:
Science DOI: 10.1126/science.1185723
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 S?ren 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,*
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.