TY - JOUR
T1 - Redox metabolites signal polymicrobial biofilm development via the napa oxidative stress cascade in aspergillus
AU - Zheng, He
AU - Kim, Jaekuk
AU - Liew, Mathew
AU - Yan, John K.
AU - Herrera, Oscar
AU - Bok, Jin Woo
AU - Kelleher, Neil L.
AU - Keller, Nancy P.
AU - Wang, Yun
N1 - Funding Information:
We thank D.A. Hogan for the PA14 phzM ::Tn M strain; J.-F. Gaillard for inputs on cyclic voltammetry experiments; and Y. Jiao and Y.W. laboratory members for discussions. This work was supported by startup and ISEN funding from Northwestern University (to Y.W.), NIH Grant R01 GM 067725 (to N.L.K.), and National Science Foundation Grant Emerging Frontiers in Research and Innovation 1136903 (to N.P.K.).
Publisher Copyright:
© 2015 Elsevier Ltd. All rights reserved.
PY - 2015/1/5
Y1 - 2015/1/5
N2 - Background 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.Results Here, we report that these "toxins" can act as interspecies signals, affecting filamentous fungal development via oxidative stress regulation. Specifically, in coculture 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.Conclusions 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.
AB - Background 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.Results Here, we report that these "toxins" can act as interspecies signals, affecting filamentous fungal development via oxidative stress regulation. Specifically, in coculture 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.Conclusions 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.
UR - http://www.scopus.com/inward/record.url?scp=84920573508&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84920573508&partnerID=8YFLogxK
U2 - 10.1016/j.cub.2014.11.018
DO - 10.1016/j.cub.2014.11.018
M3 - Article
C2 - 25532893
AN - SCOPUS:84920573508
VL - 25
SP - 29
EP - 37
JO - Current Biology
JF - Current Biology
SN - 0960-9822
IS - 1
ER -