title: Pseudomonas aeruginosa manipulates redox and iron homeostasis of its microbiota partner Aspergillus fumigatus via phenazines.
abstract: The opportunistic fungal pathogen Aspergillus fumigatus is increasingly found as a coinfecting agent along with Pseudomonas aeruginosa in cystic fibrosis patients. Amongst the numerous molecules secreted by P. aeruginosa during its growth, phenazines constitute a major class. P. aeruginosa usually secreted four phenazines, pyocyanin (PYO), phenazine-1-carboxamide (PCN), 1-hydroxyphenazine (1-HP) and phenazine-1-carboxylic acid (PCA). These phenazines inhibited the growth of A. fumigatus but the underlying mechanisms and the impact of these four phenazines on A. fumigatus biology were not known. In the present study, we analyzed the functions of the four phenazines and their mode of action on A. fumigatus. All four phenazines showed A. fumigatus growth inhibitory effects by inducing production of reactive oxygen species (ROS), specifically O2(·-), and reactive nitrogen species (RNS), ONOO(-). A. fumigatus Sod2p was the major factor involved in resistance against the ROS and RNS induced by phenazines. Sub-inhibitory concentrations of PYO, PCA and PCN promote A. fumigatus growth by an independent iron-uptake acquisition. Of the four phenazines 1-HP had a redox-independent function; being able to chelate metal ions 1-HP induced A. fumigatus iron starvation. Our data show the fine-interactions existing between A. fumigatus and P. aeruginosa, which can lead to stimulatory or antagonistic effects.
authors: 1] Unité des Aspergillus Institut Pasteur, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, Paris, France.
authors: Benoit
authors: B
authors: Briard
authors: Plateforme de microscopie ultrastructurale, Institut Pasteur, Paris, France.
authors: Perrine
authors: P
authors: Bomme
authors: Biocenter-Division of Molecular Biology, Innsbruck Medical University, Innsbruck, Austria.
authors: Beatrix E
authors: BE
authors: Lechner
authors: UMR 7242 Biotechnologie et Signalisation Cellulaire, Université de Strasbourg-CNRS, France.
authors: Gaëtan L A
authors: GL
authors: Mislin
authors: PSL Research University, Chimie ParisTech-CNRS, Institut de Recherche de Chimie Paris, 75005, Paris, France.
authors: Virginie
authors: V
authors: Lair
authors: Plateforme de microscopie ultrastructurale, Institut Pasteur, Paris, France.
authors: Marie-Christine
authors: MC
authors: Prévost
authors: Unité des Aspergillus Institut Pasteur, Paris, France.
authors: Jean-Paul
authors: JP
authors: Latgé
authors: Biocenter-Division of Molecular Biology, Innsbruck Medical University, Innsbruck, Austria.
authors: Hubertus
authors: H
authors: Haas
authors: Unité des Aspergillus Institut Pasteur, Paris, France.
authors: Anne
authors: A
authors: Beauvais
mesh_terms: D001232:Aspergillus fumigatus / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D064307:Microbiota / Q000502:physiology*; D010084:Oxidation-Reduction; D010619:Phenazines / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D010619:Phenazines; D026361:Reactive Nitrogen Species; D013481:Superoxides; D007501:Iron