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.

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 O₂̇ˉ, 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.

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.