Aspergillus fumigatus protein phosphatase PpzA is involved in iron assimilation, secondary metabolite production, and virulence. (17th August 2017)

• Record Type: Journal Article
• Authors: Manfiolli, Adriana Oliveira; de Castro, Patrícia Alves; dos Reis, Thaila Fernanda; Dolan, Stephen; Doyle, Sean; Jones, Gary; Riaño Pachón, Diego M.; Ulaş, Mevlüt; Noble, Luke M.; Mattern, Derek J.; Brakhage, Axel A.; Valiante, Vito; Silva‐Rocha, Rafael; Bayram, Ozgur; Goldman, Gustavo H.
• Is Part Of: Cellular microbiology. Volume 19:Number 12(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-08-17
• Subjects: Microbiology -- Periodicals; Cytology -- Periodicals; Host-parasite relationships -- Periodicals; Microbiology -- Periodicals; Cells -- Periodicals; Microbiologie -- Périodiques; Microbiologie; Relation hôte-parasite; Cytologie; Cellule; Réponse cellulaire; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); 579.05
• DOI: 10.1111/cmi.12770
• Languages: English
• ISSNs: 1462-5814

Abstract

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 .