The Natural Product Elegaphenone Potentiates Antibiotic Effects against Pseudomonas aeruginosa
The Natural Product Elegaphenone Potentiates Antibiotic Effects against Pseudomonas aeruginosa
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天然产物刺猬酮增强对铜绿假单胞菌的抗生素作用
DOI：
10.1002/anie.201903472
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Medina, Eva
中科院分区：
文献类型：
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作者：
Zhao, Weining;Cross, Ashley R.;Crowe‐McAuliffe, Caillan;Weigert‐Munoz, Angela;Csatary, Erika E.;Solinski, Amy E.;Krysiak, Joanna;Goldberg, Joanna B.;Wilson, Daniel N.;Medina, Eva
天然产物代表了针对多功能细胞靶点的抗生素的丰富来源。通过化学蛋白质组学对它们的靶点进行去卷积常常受到大的光交联剂的引入的挑战。在这里，我们应用了elegaphenone，一种带有天然二苯甲酮核心支架的大部分未表征的天然产物抗生素，用于革兰氏阳性和革兰氏阴性细菌中基于亲和力的蛋白质谱分析（AfBPP）。本研究利用炔基化的天然产物支架作为探针，以揭示与转录调节因子AlgP的有趣的生物相互作用。此外，铜绿假单胞菌AlgP转座子突变体的蛋白质组分析提供了独特的见解的作用模式。Elegaphenone增强了暴露于亚抑制浓度的氟喹诺酮类抗生素诺氟沙星的胞内铜绿假单胞菌巨噬细胞的消除。
Natural products represent a rich source of antibiotics that address versatile cellular targets. The deconvolution of their targets via chemical proteomics is often challenged by the introduction of large photocrosslinkers. Here we applied elegaphenone, a largely uncharacterized natural product antibiotic bearing a native benzophenone core scaffold, for affinity‐based protein profiling (AfBPP) in Gram‐positive and Gram‐negative bacteria. This study utilizes the alkynylated natural product scaffold as a probe to uncover intriguing biological interactions with the transcriptional regulator AlgP. Furthermore, proteome profiling of a Pseudomonas aeruginosa AlgP transposon mutant provided unique insights into the mode of action. Elegaphenone enhanced the elimination of intracellularP. aeruginosain macrophages exposed to sub‐inhibitory concentrations of the fluoroquinolone antibiotic norfloxacin.