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研究发现针对革兰氏阴性菌的新抗生素
2019-11-21 12:41

美国东北大学Kim Lewis研究团队,发现一种新的抗生素可以选择性地杀死革兰氏阴性病原体。该研究11月20日在线发表在《自然》上。

研究人员从发光杆菌分离株的筛选物中发现了一种新抗生素,并命名为darobactin。darobactin由沉默的操纵子编码并由核糖体合成,其在实验室条件下几乎不产生。darobactin具有独特的结构,其带有两个在翻译后形成的稠合环。该化合物在体外和动物感染模型中均对主要的革兰氏阴性病原体具有活性。darobactin的突变体可映射到BamA,BamA是外膜蛋白折叠必不可少的分子伴侣和易位蛋白。这项的研究表明,动物的细菌共生体内含有适合发展为治疗剂的抗生素。

研究人员表示,当前研究针对耐药性革兰氏阴性病原体的新型抗生素迫在眉睫。这些微生物具有高度限制性的通透屏障,该屏障阻碍了大多数化合物的渗透。因此,在20世纪60年代才研发出针对革兰氏阴性细菌的抗生素。研究者认为,可以在与人类对抗生素具有相似需求的细菌中发现有用的化合物,并着重于致病性线虫微生物群的发光杆菌共生体。

附:英文原文

Title: A new antibiotic selectively kills Gram-negative pathogens

Author: Yu Imai, Kirsten J. Meyer, Akira Iinishi, Quentin Favre-Godal, Robert Green, Sylvie Manuse, Mariaelena Caboni, Miho Mori, Samantha Niles, Meghan Ghiglieri, Chandrashekhar Honrao, Xiaoyu Ma, Jason Guo, Alexandros Makriyannis, Luis Linares-Otoya, Nils Bhringer, Zerlina G. Wuisan, Hundeep Kaur, Runrun Wu, Andre Mateus, Athanasios Typas, Mikhail M. Savitski, Josh L. Espinoza, Aubrie ORourke, Karen E. Nelson, Sebastian Hiller, Nicholas Noinaj, Till F. Schberle, Anthony DOnofrio, Kim Lewis

Issue&Volume: 2019-11-20

Abstract: The current need for novel antibiotics is especially acute for drug-resistant Gram-negative pathogens1,2. These microorganisms have a highly restrictive permeability barrier, which limits the penetration of most compounds3,4. As a result, the last class of antibiotics acting against Gram-negative bacteria was developed in the 1960s2. We reason that useful compounds can be found in bacteria that share similar requirements for antibiotics with humans, and focus on Photorhabdus symbionts of entomopathogenic nematode microbiomes. Here we report a new antibiotic that we name darobactin, from a screen of Photorhabdus isolates. Darobactin is coded by a silent operon with little production under laboratory conditions, and is ribosomally synthesized. Darobactin has an unusual structure with two fused rings that form post-translationally. The compound is active against important Gram-negative pathogens both in vitro and in animal models of infection. Mutants resistant to darobactin map to BamA, an essential chaperone and translocator that folds outer membrane proteins. Our study suggests that bacterial symbionts of animals contain antibiotics that are particularly suitable for development into therapeutics.

DOI: 10.1038/s41586-019-1791-1

Source:https://www.nature.com/articles/s41586-019-1791-1

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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