Aspergillus fumigatus protein phosphatase PpzA is involved in iron assimilation, secondary metabolite production, and virulence. (17th August 2017) - Manfiolli, Adriana Oliveira
Summary: Metal restriction imposed by mammalian hosts during an infection is a common mechanism of defence to reduce or avoid the pathogen infection. Metals are essential for organism survival due to its involvement in several biological processes. Aspergillus fumigatus causes invasive aspergillosis, a disease that typically manifests in immunocompromised patients. A . fumigatus PpzA, the catalytic subunit of protein phosphatase Z (PPZ), has been recently identified as associated with iron assimilation. A . fumigatus has 2 high‐affinity mechanisms of iron acquisition during infection: reductive iron assimilation and siderophore‐mediated iron uptake. It has been shown that siderophore production is important for A . fumigatus virulence, differently to the reductive iron uptake system. Transcriptomic and proteomic comparisons between ∆ppzA and wild‐type strains under iron starvation showed that PpzA has a broad influence on genes involved in secondary metabolism. Liquid chromatography‐mass spectrometry under standard and iron starvation conditions confirmed that the Δ ppzA mutant had reduced production of pyripyropene A, fumagillin, fumiquinazoline A, triacetyl‐fusarinine C, and helvolic acid. The Δ ppzA was shown to be avirulent in a neutropenic murine model of invasive pulmonary aspergillosis. PpzA plays an important role at the interface between iron starvation, regulation of SM production, and pathogenicity in A . fumigatus .