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NRPS-Derived Isoquinolines and Lipopetides Mediate Antagonism between Plant Pathogenic Fungi and Bacteria
ACS Chemical Biology ( IF 4 ) Pub Date : 2017-12-18 00:00:00 , DOI: 10.1021/acschembio.7b00731
Saima Khalid 1, 2 , Joshua A. Baccile 3 , Joseph E. Spraker 4 , Joanna Tannous 1 , Muhammad Imran 2 , Frank C. Schroeder 3 , Nancy P. Keller 1
Affiliation  

Bacterial–fungal interactions are presumed to be mediated chiefly by small-molecule signals; however, little is known about the signaling networks that regulate antagonistic relationships between pathogens. Here, we show that the ralstonins, lipopeptides produced by the plant pathogenic bacteria Ralstonia solanacearum, interfere with germination of the plant-pathogenic fungus Aspergillus flavus by down-regulating expression of a cryptic biosynthetic gene cluster (BGC), named imq. Comparative metabolomic analysis of overexpression strains of the transcription factor ImqK revealed imq-dependent production of a family of tripeptide-derived alkaloids, the imizoquins. These alkaloids are produced via a nonribosomal peptide synthetase- (NRPS-)derived tripeptide and contain an unprecedented tricyclic imidazo[2,1-a]isoquinoline ring system. We show that the imizoquins serve a protective role against oxidative stress that is essential for normal A. flavus germination. Supplementation of purified imizoquins restored wildtype germination to a ΔimqK A. flavus strain and protected the fungus from ROS damage. Whereas the bacterial ralstonins retarded A. flavus germination and suppressed expression of the imq cluster, the fungal imizoquins in turn suppressed growth of R. solanacearum. We suggest such reciprocal small-molecule-mediated antagonism is a common feature in microbial encounters affecting pathogenicity and survival of the involved species.

中文翻译:

NRPS衍生的异喹啉和脂肽介导植物病原真菌和细菌之间的拮抗作用。

据推测,细菌-真菌相互作用主要是由小分子信号介导的。然而,对于调节病原体之间拮抗关系的信号网络知之甚少。在这里,我们显示了植物病原细菌Ralstonia solanacearum产生的拉尔斯通素,脂肽,通过下调隐匿性生物合成基因簇(BGC)的表达(imq)来干扰植物病原性真菌黄曲霉的发芽。对转录因子ImqK的过表达菌株进行的比较代谢组学分析表明,三肽衍生生物碱家族亚基咪唑喹啉依赖于imq。这些生物碱是通过非核糖体肽合成酶-(NRPS-)衍生的三肽,并包含前所未有的三环咪唑并[2,1- a ]异喹啉环系统。我们表明,咪唑喹类对氧化应激具有保护作用,而氧化应激对于正常的黄曲霉种子萌发是必不可少的。补充纯化的咪唑喹使野生型萌发恢复为ΔimqK A.黄曲霉菌株,并保护真菌免受ROS损害。细菌性的雷尔司汀可延缓黄曲霉的萌发并抑制imq簇的表达,而真菌的咪唑喹反过来又可抑制茄形毛霉的生长。我们建议这种相互的小分子介导的拮抗作用是影响所涉及物种的致病性和生存的微生物接触中的共同特征。
更新日期:2017-12-18
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