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. 2015 Feb 10;5:8220. doi: 10.1038/srep08220

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The four major phenazines of P. aeruginosa bind to hyphae and penetrate the cell. Few PCA penetrates due its negative charge (Lime green pathway,). Phenazines act at the level of mitochondria and induce the production of superoxide anion (O₂^·−) and peroxynitrite (ONOO⁻) (Red pathway,). MnSod2p enzyme converts O₂^·− to hydrogen peroxide (H₂O₂) and a catalase-independent mechanism allows its detoxification into H₂O. The anion ONOO⁻ formed from O₂^·− and nitric oxide (NO^·) is also detoxified by MnSod2p (Red pathway,). PYO, PCN and PCA reduce Fe(III) to Fe(II) which penetrates the A. fumigatus cell through the iron ferroxidase FetCp/permease FtrAp complex (Green pathway,). 1-HP also reduces Fe(III) to Fe(II) and two 1-HP molecules can chelate the newly formed Fe(II) (Orange pathway,). This chelating activity induces iron starvation which causes HapXp activation. The biosynthetic pathway of triacetylfusarinine C (TAFC) is then activated and allows Fe³⁺ acquisition to stimulate the growth of the fungus (Orange pathway,).

Inline graphic — The four major phenazines of P. aeruginosa bind to hyphae and penetrate the cell. Few PCA penetrates due its negative charge (Lime green pathway,). Phenazines act at the level of mitochondria and induce the production of superoxide anion (O₂^·−) and peroxynitrite (ONOO⁻) (Red pathway,). MnSod2p enzyme converts O₂^·− to hydrogen peroxide (H₂O₂) and a catalase-independent mechanism allows its detoxification into H₂O. The anion ONOO⁻ formed from O₂^·− and nitric oxide (NO^·) is also detoxified by MnSod2p (Red pathway,). PYO, PCN and PCA reduce Fe(III) to Fe(II) which penetrates the A. fumigatus cell through the iron ferroxidase FetCp/permease FtrAp complex (Green pathway,). 1-HP also reduces Fe(III) to Fe(II) and two 1-HP molecules can chelate the newly formed Fe(II) (Orange pathway,). This chelating activity induces iron starvation which causes HapXp activation. The biosynthetic pathway of triacetylfusarinine C (TAFC) is then activated and allows Fe³⁺ acquisition to stimulate the growth of the fungus (Orange pathway,).