Aspergillus fumigatus protein phosphatase PpzA is involved in iron assimilation, secondary metabolite production, and virulence

Cell Microbiol. 2017 Dec;19(12). doi: 10.1111/cmi.12770. Epub 2017 Aug 17.

Abstract

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 ΔppzA mutant had reduced production of pyripyropene A, fumagillin, fumiquinazoline A, triacetyl-fusarinine C, and helvolic acid. The ΔppzA 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspergillus fumigatus / enzymology*
  • Aspergillus fumigatus / genetics
  • Aspergillus fumigatus / metabolism
  • Aspergillus fumigatus / pathogenicity*
  • Chromatography, Liquid
  • Disease Models, Animal
  • Gene Deletion
  • Gene Expression Profiling
  • Invasive Pulmonary Aspergillosis / microbiology
  • Invasive Pulmonary Aspergillosis / pathology
  • Iron / metabolism*
  • Mass Spectrometry
  • Metabolomics
  • Mice
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism*
  • Proteome / analysis
  • Secondary Metabolism*
  • Virulence

Substances

  • Proteome
  • Iron
  • Phosphoprotein Phosphatases