Plectasin is a peptide antibiotic with therapeutic potential from a saprophytic fungus
Plectasin is a peptide antibiotic with therapeutic potential from a saprophytic fungus
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DOI：
10.1038/nature04051
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发表时间：
2005-10-13
期刊：
影响因子：
64.8
通讯作者：
Kristensen, HH
中科院分区：
文献类型：
--
作者：
Mygind, PH;Fischer, RL;Kristensen, HH
动物和高等植物表达称为防御素的内源性肽抗生素。这些富含半胱氨酸的小肽具有抗细菌、真菌和病毒的活性。在这里，我们描述了plectasin --第一个从真菌（腐生子囊菌Pseudoplectania nigrella）中分离出来的防御素。Plectasin具有与蜘蛛、蝎子、蜻蜓和贻贝中发现的防御素非常相似的一级、二级和三级结构。重组plectasin以非常高且商业上可行的产率和纯度产生。在体外，重组肽对肺炎链球菌特别有效，包括对常规抗生素耐药的菌株。百菌清对小鼠毒性极低，对实验性腹膜炎和肺炎均有治疗作用。与万古霉素和青霉素一样有效。这些发现确定真菌作为一种新的来源的抗菌防御素，并显示了治疗潜力的plectasin。他们还认为，昆虫、软体动物和真菌的防御素来自一个共同的祖先基因。
Animals and higher plants express endogenous peptide antibiotics called defensins. These small cysteine-rich peptides are active against bacteria, fungi and viruses. Here we describe plectasin - the first defensin to be isolated from a fungus, the saprophytic ascomycete Pseudoplectania nigrella. Plectasin has primary, secondary and tertiary structures that closely resemble those of defensins found in spiders, scorpions, dragonflies and mussels. Recombinant plectasin was produced at a very high, and commercially viable, yield and purity. In vitro, the recombinant peptide was especially active against Streptococcus pneumoniae, including strains resistant to conventional antibiotics. Plectasin showed extremely low toxicity in mice, and cured them of experimental peritonitis and pneumonia caused by S. pneumoniae as efficaciously as vancomycin and penicillin. These findings identify fungi as a novel source of antimicrobial defensins, and show the therapeutic potential of plectasin. They also suggest that the defensins of insects, molluscs and fungi arose from a common ancestral gene.