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一对细菌铁载体释放并捕获细胞间信号分子:天然亚硝酮生物缀合的一个不寻常案例。

A Pair of Bacterial Siderophores Releases and Traps an Intercellular Signal Molecule: An Unusual Case of Natural Nitrone Bioconjugation.

机构信息

Department of Biomolecular Chemistry, Leibniz Institute, for Natural Product Chemistry and Infection Biology (HKI), Beutenbergstrasse 11a, 07745, Jena, Germany.

Natural Product Chemistry, Faculty of Biological Sciences, Friedrich Schiller University Jena, 07743, Jena, Germany.

出版信息

Angew Chem Int Ed Engl. 2019 Jan 2;58(1):200-204. doi: 10.1002/anie.201811131. Epub 2018 Dec 4.

Abstract

In microbial interactions bacteria employ diverse molecules with specific functions, such as sensing the environment, communication with other microbes or hosts, and conferring virulence. Insights into the molecular basis of bacterial communication are thus of high relevance for ecology and medicine. Targeted gene activation and in vitro studies revealed that the cell-to-cell signaling molecule and disease mediator IQS (aeruginaldehyde) of the human pathogen Pseudomonas aeruginosa and related bacteria derives from the siderophore pyochelin. Addition of IQS to bacterial cultures (Burkholderia thailandensis) showed that the signaling molecule is captured by a congener of another siderophore family, malleobactin, to form a nitrone conjugate (malleonitrone) that is active against the IQS-producer. This study uncovers complex communication processes with derailed siderophore functions, a novel nitrone bioconjugation, and a new type of antibiotic against Gram-negative bacteria.

摘要

在微生物相互作用中,细菌会使用具有特定功能的多种分子,例如感知环境、与其他微生物或宿主进行通信以及赋予毒性。因此,深入了解细菌通信的分子基础对于生态学和医学具有重要意义。靶向基因激活和体外研究表明,人类病原体铜绿假单胞菌和相关细菌的细胞间信号分子和疾病介质 IQS(绿脓菌素)源自铁载体吡咯并[1,2-α]喹喔啉。将 IQS 添加到细菌培养物(泰国伯克霍尔德菌)中表明,该信号分子被另一种铁载体家族的同系物马莱菌素捕获,形成具有活性的亚硝酮缀合物(马莱硝酮)针对 IQS 产生菌。这项研究揭示了具有脱轨铁载体功能的复杂通信过程、新型亚硝酮生物缀合以及针对革兰氏阴性菌的新型抗生素。

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