5月27日，德國波恩大學科學家報告說,，他們與丹麥和荷蘭科學家合作發(fā)現(xiàn)了一種新型抗菌肽——菌絲霉素的抗菌機理,。科學家認為這種抗菌肽有望在新型抗菌素研發(fā)中發(fā)揮主導作用,。
菌絲霉素是丹麥生物技術(shù)公司數(shù)年前從真菌中分離出的一種防御素,。防御素是存在于動物和高等植物中的一類富含半胱氨酸的天然抗菌肽，它們對多種微生物均具有較強的防御能力,，因此,，防御素也是目前頗具吸引力的一類新型候選抗菌藥物。
科學家們此次發(fā)現(xiàn),，菌絲霉素與細菌細胞膜形成的前體物質(zhì)Lipid Ⅱ具有很強的親和性,，可以通過與Lipid Ⅱ結(jié)合阻止病菌細胞膜的形成，從而阻止病菌繁殖,。
德國科學家指出,，菌絲霉素的抗菌方式類似于現(xiàn)在廣泛使用的藥物萬古霉素。后者20年來在對抗具有頑固抗藥性的耐甲氧西林金黃色葡萄球菌領(lǐng)域發(fā)揮了重要作用,。但是,，近年來越來越多的病菌對萬古霉素也產(chǎn)生了抗藥性，對菌絲霉素則依然敏感,，因而菌絲霉素成了研制新型抗菌藥的希望之星,。
但是德國科學家同時指出,，菌絲霉素也不能一勞永逸地解決病菌抗藥性問題。病菌逐步變異,，對新藥物產(chǎn)生抗藥性只是時間問題,。人類與病菌之間永遠存在“軍備競賽”。(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.
