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:
影响因子:
--
通讯作者:
Wang Y
中科院分区:
文献类型:
--
作者:
Zheng H;Kim J;Liew M;Yan JK;Herrera O;Bok JW;Kelleher NL;Keller NP;Wang Y
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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