Redox metabolites signal polymicrobial biofilm development via the NapA oxidative stress cascade in Aspergillus.

Redox metabolites signal polymicrobial biofilm development via the NapA oxidative stress cascade in Aspergillus.
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DOI:
10.1016/j.cub.2014.11.018
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发表时间:
2015-01-05
期刊:
Current biology : CB
影响因子:
--
通讯作者:
Wang Y
Wang Y
中科院分区:
其他
文献类型:
--
作者:
Zheng H;Kim J;Liew M;Yan JK;Herrera O;Bok JW;Kelleher NL;Keller NP;Wang Y

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丝状真菌和细菌在自然界和不同的临床环境中形成混合物种生物膜。它们分泌大量氧化还原活性的小分子次生代谢物,传统上被视为抑制竞争微生物生长的毒素。在这里,我们报告了这些“毒素”可以作为物种间的信号,通过氧化应激调节影响丝状真菌的发育。具体地说,在共培养生物膜中,铜绿假单胞菌吩嗪衍生的代谢物差异化地调节烟曲霉的发育,沿着吩嗪递减的梯度从弱营养生长转移到诱导无性产孢子(分生)。烟曲霉菌的形态漂移与吩嗪自由基的产生和吩嗪氧化还原循环产生的活性氧(ROS)有关。吩嗪分生孢子信号在nidulans的遗传模型中是保守的,并由napA介导,napA是AP-1样bZIP转录因子的同源物,在人类、酵母和丝状真菌对氧化应激的反应中是必不可少的。表达谱显示,吩嗪治疗诱导了全球氧化应激代谢组的NAPA依赖的反应,包括硫氧还蛋白、谷胱甘肽和NADPH-氧化酶系统。另一种微生物氧化还原活性次生代谢物--胶质毒素也需要napA才能诱导根瘤拟青霉分生孢子。这项工作强调了微生物氧化还原代谢产物是丝状真菌孢子形成的关键信号,这些信号通过进化保守的真核细胞应激反应途径进行交流。它为涉及细菌和丝状真菌的环境和临床生物膜中的物种间信号转导提供了基础。
Filamentous fungi and bacteria form mixed-species biofilms in nature and diverse clinical contexts. They secrete a wealth of redox-active small molecule secondary metabolites, which are traditionally viewed as toxins that inhibit growth of competing microbes. Here we report that these “toxins” can act as interspecies signals, affecting filamentous fungal development via oxidative stress regulation. Specifically, in co-culture biofilms, Pseudomonas aeruginosa phenazine-derived metabolites differentially modulated Aspergillus fumigatus development, shifting from weak vegetative growth to induced asexual sporulation (conidiation) along a decreasing phenazine gradient. The A. fumigatus morphological shift correlated with the production of phenazine radicals and concomitant reactive oxygen species (ROS) production generated by phenazine redox cycling. Phenazine conidiation signaling was conserved in the genetic model A. nidulans, and mediated by NapA, a homolog of AP-1-like bZIP transcription factor, which is essential for the response to oxidative stress in humans, yeast, and filamentous fungi. Expression profiling showed phenazine treatment induced a NapA-dependent response of the global oxidative stress metabolome including the thioredoxin, glutathione and NADPH-oxidase systems. Conidiation induction in A. nidulans by another microbial redox-active secondary metabolite, gliotoxin, also required NapA. This work highlights that microbial redox metabolites are key signals for sporulation in filamentous fungi, which are communicated through an evolutionarily conserved eukaryotic stress response pathway. It provides a foundation for interspecies signaling in environmental and clinical biofilms involving bacteria and filamentous fungi.
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