Pseudomonas aeruginosa manipulates redox and iron homeostasis of its microbiota partner Aspergillus fumigatus via phenazines

Benoit Briard,Perrine Bomme,Beatrix Lechner,Gaëtan Mislin,Virginie Lair,Marie-Christine Prévost,Jean-Paul Latgé,Hubertus Haas,Anne Beauvais

doi:10.1016/j.mycmed.2015.02.026

Abstract

Background 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. Previous studies have demonstrated that P. aeruginosa 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. Results In the present study, we analyzed the functions of the four phenazines produced by P. aeruginosa and their mode of action on growth and survival of A. fumigatus . All four phenazines showed A. fumigatus growth inhibitory effects by inducing production of reactive oxygen species (ROS), specifically O 2 ˉ, and reactive nitrogen species (RNS), ONOOˉ. 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. Conclusions Our data show the fine-interactions existing between A. fumigatus and P. aeruginosa , the latter limiting the growth of A. fumigatus by ROS and RNS productions and iron chelation but also favouring the growth by facilitating iron-uptake by the fungus under iron starvation.

Highlights

To cite this version: Benoit Briard, Perrine Bomme, Beatrix E
Four main phenazines have been identified in P. aeruginosa: Phenazine-1-carboxylic acid (Phenazine-1-carboxylate, phenazine-1-carboxylic acid (PCA)), which is produced from chorismic acid
We found that A. fumigatus Sod2p was the major factor involved in resistance against the reactive oxygen species (ROS) and reactive nitrogen species (RNS) induced by phenazines

Summary

Introduction

To cite this version: Benoit Briard, Perrine Bomme, Beatrix E. 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. Phenazines are small diffusible quorum sensing molecules which penetrate all kind of cells[1] These natural pigments comprise blue for pyocyanin (PYO), yellow for phenazine-1-carboxylic acid (PCA) and phenazine-1-carboxamide (PCN) and orange for 1-hydroxyphenazine (1-HP). They are considered as the main virulence factor of P. aeruginosa against a broad range of target organisms, including other bacteria, fungi and mammalian cells[1,2,3]. Phenazines are endogenous redox-active molecules and it has been demonstrated that this activity promotes P. aeruginosa growth and survival under iron limiting conditions, as in cystic fibrosis

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Conclusion